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P Alaupovic

Publications and source records attributed to P Alaupovic.

At least 37 records · Page 2Linked to original sources
PubMed1997

The role of triglyceride-rich lipoprotein families in the progression of atherosclerotic lesions as determined by sequential coronary angiography from a controlled clinical trial.

We have demonstrated previously in a subset of Monitored Atherosclerosis Regression Study (MARS) subjects with hypercholesterolemia (190 to 295 mg/dL) and documented coronary artery disease that lovastatin significantly reduces cholesterol-rich lipoprotein B (LpB) but has little effect on complex, triglyceride-rich apolipoprotein (apo) B-containing LpBc (the sum of LpB:C, LpB:C:E and LpA-II:B:C:D:E) particles defined by their apolipoprotein composition. This differential effect of lovastatin on apoB-containing lipoprotein families offered the opportunity to determine in the same subset of MARS subjects the independent relationship of LpB and LpBc with the progression of coronary artery disease. Subjects randomized to either lovastatin (40 mg twice daily) or matching placebo were evaluated by coronary angiography before randomization and after 2 years of treatment, and the overall coronary status was judged by a coronary global change score. In the lovastatin-treated group, there were 22 nonprogressors (69%) and 10 progressors (31%), while in the placebo group 13 subjects (42%) were nonprogressors and 18 (58%) were progressors (P < .03). In the lovastatin-treated group, lipid and lipoprotein parameters did not differ between progressors and nonprogressors except for LpBc and LpA-II:B:C:D:E particle levels, which were statistically higher in progressors (P = .02). In the placebo-treated group, progressors differed from nonprogressors by having significantly higher levels of triglycerides (P = .03) and apoC-III in VLDL + LDL (P = .05), the characteristic constituents of triglyceride-rich lipoproteins. In the placebo- and lovastatin-treated groups combined, progressors had significantly higher on-trial levels of triglycerides (P = .003), VLDL cholesterol (P = .005), apoC-III in VLDL + LDL (P = .008), apoC-III (P = .01), apoB (P = .03), and total cholesterol (P = .04) than nonprogressors. Even after adjustment for treatment group, progressors in the combined placebo- and lovastatin-treated groups had significantly higher levels of LpBc, LpA-II:B:C:D:E, triglycerides, and apoC-III in VLDL + LDL than nonprogressors. Progressors in the placebo-treated, lovastatin-treated, and combined treatment groups had lower levels of LpA-1 but not LpA-I:A-II than non-progressors, and this difference reached statistical significance (P = .047) in the combined sample adjusted for treatment group. Results of this study show that elevated levels of triglyceride-rich LpBc in general and LpA-II:B:C:D:E in particular contribute significantly to the progression of coronary artery disease. Furthermore, they provide additional evidence for the potentially protective role of LpA-I particles in the atherogenic process and suggest that apolipoprotein-defined lipoprotein families may be more specific prognosticators of coronary artery atherosclerosis progression than lipids and apolipoproteins.

Adult↗
PubMed1997

Efficacy and safety of a new hydroxymethylglutaryl-coenzyme A reductase inhibitor, atorvastatin, in patients with combined hyperlipidemia: comparison with fenofibrate.

This 24-week, randomized, open-label multicenter study evaluated the efficacy and safety of atorvastatin compared with fenofibrate in the treatment of patients with combined hyperlipidemia (CHL). Following a 6-week baseline period, 84 patients with CHL were randomly assigned to either atorvastatin treatment, 10 mg QD for 12 weeks increasing to 20 mg QD for 12 weeks, or fenofibrate treatment, 100 mg TID for 24 weeks. Changes from baseline in lipid parameters were evaluated at weeks 12 and 24. At both 10- and 20-mg doses, atorvastatin treatment resulted in significantly greater reductions in LDL cholesterol, apolipoprotein (apo) B, total cholesterol, LDL-apoB, and lipoprotein-B compared to 300-mg fenofibrate treatment (P < .05). While atorvastatin also resulted in clinically significant reductions in triglyceride, VLDL cholesterol, apoB in VLDL, triglyceride in VLDL, and apoC-III and significant increases in HDL cholesterol and apoA-I levels, fenofibrate was more effective than atorvastatin in altering all these parameters. However, by significantly affecting both the cholesterol-rich and triglyceride-rich particles, atorvastatin holds promise as a lipid-regulator able to adequately treat a broad range of patients that includes those with CHL.

Adult↗
PubMed1997

Progression of renal failure: role of apolipoprotein B-containing lipoproteins.

Plasma lipoproteins (LP) may be identified on the basis of density properties or apolipoprotein (apo) composition. ApoB-containing LP occur in VLDL, IDL and LDL. There are several types of apoB-containing LP characterized by specific composition of minor apolipoproteins (apoC, apoE etc.) and lipid constituents (triglycerides and cholesterol), metabolic properties and relative atherogenicity. The alterations of lipoprotein metabolism in renal disease resulting in elevated levels of apoB-containing LP may be reflected in hyperlipidemia. Whereas nephrotic syndrome and heavy proteinuria are associated with increased formation of cholesterol-rich apoB-containing LP in LDL and VLDL, the characteristic feature in renal failure is the accumulation of intact or partially metabolised triglyceride-rich LP in IDL and VLDL. The potentially atherogenic apoB-containing LP have been linked to the pathogenic processes that result in progressive glomerular and interstitial lesions and ultimate loss of renal function. The mechanisms of injury are not fully understood. Receptor- and non-receptor mediated uptake of LP by mesangial cells may induce or accelerate proliferative and sclerotic processes in the glomerular mesangium that are analogous to atherosclerosis in the arterial wall. Changes in glomerular permeability can result in increased filtration of LP that may be internalized by tubular cells and elicit corresponding lesions in the interstitial tissues. The negative impact of proteinuria on the prognosis of renal disease could be mediated in part through an increased filtration of lipoproteins. Induction of hyperlipidemia accelerates glomerular and interstitial damage in experimental renal failure. This can be attenuated by treatment with hypolipemic agents. In patients, increased concentrations of apoB-containing LP are associated with more rapid progression of renal insufficiency in both primary renal disease and diabetic nephropathy. It is, however, presently not known to what extent treatment of the renal dyslipidemia can modify the progression of chronic renal failure. Experimental and clinical evidence suggest that apoB-containing LP may play a pathogenetic role in the progression of renal disease.

Apolipoproteins B↗
PubMed1996

Triglyceride enriched lipoprotein particles correlate with the severity of coronary artery disease.

A group of 100 male normotensive, non-obese, non-diabetic subjects who had undergone coronary angiography were studied to determine relationship between the severity of coronary artery disease (CAD) and plasma lipids, apolipoproteins and lipoprotein particles defined by their apolipoprotein composition. CAD was found in 84 and no measurable lesions were found in 26 subjects. The severity of CAD was determined on the basis of size and number of lesions and expressed in terms of a global CAD score. Low density lipoprotein (LDL)-cholesterol showed a tendency to be higher in CAD patients than in CAD-free subjects (216 vs. 205 mg/dl, P = 0.07). HDL-cholesterol showed a tendency towards lower values in CAD patients compared to CAD-free subjects 35 vs. 41 mg/dl, P = 0.07). In univariate analysis the severity of CAD correlated with (i) complex, apolipoprotein (apo) B containing particles (Lp-B-complex, r = 0.31, P = 0.005), (ii) HDL-cholesterol (r = -0.30, P = 0.005), (iii) apoC-III in heparin precipitate (r = 0.30, P = 0.005) and (iv) plasma triglycerides (r = 0.25, P = 0.02), all of which are related to triglyceride-rich lipoproteins. A comparison between the two subspecies of complex lipoprotein particles revealed that those containing apolipoproteins B, C-III and E (Lp-B:C:E complex) were more closely associated with CAD score (r = 0.27, P = 0.01) than those containing apolipoproteins A-II, B, C, D and E (Lp-A-II:B-complex). LDL-cholesterol also correlated with the global CAD score (r = 0.23, P = 0.03). In multiple regression analysis only HDL-cholesterol (P = 0.003), apoC-III-ratio (P = 0.007), Lp-B-complex (P = 0.02) and Lp-B:C:E-complex (P = 0.04) showed significant correlation with CAD score. The results of this study demonstrate that some of the triglyceride rich lipoprotein particles represent a risk factor for CAD and support the clinical usefulness of specific assays capable of distinguishing lipoprotein particles on the basis of apolipoprotein composition.

Adult↗
PubMed1996

Reduction in carotid arterial wall thickness using lovastatin and dietary therapy: a randomized controlled clinical trial.

OBJECTIVE: To assess the effects of lipid-lowering therapy on the progression of early, preintrusive carotid arterial atherosclerosis. DESIGN: Randomized, double-blind, placebo-controlled, serial carotid arterial imaging trial. SETTING: University Atherosclerosis Research Unit. PATIENTS: 188 patients from the Monitored Atherosclerosis Regression Study who were 37 to 67 years of age and had angiographically defined coronary artery disease. INTERVENTION: Cholesterol-lowering diet plus placebo or lovastatin, 80 mg/d. MEASUREMENTS: High-resolution B-mode ultrasonographic quantification of the combined thickness of the distal common carotid arterial far wall intima-media complex (carotid arterial intima-media thickness) at baseline and every 6 months for as long as 4 years. RESULTS: The annual rate of change in carotid arterial intima-media thickness differed significantly between the lovastatin group and the placebo group at 2 and 4 years (P < 0.001). CONCLUSION: Lipid-lowering therapy reverses the progression of early, preintrusive atherosclerosis of the carotid artery. Both cholesterol-rich and triglyceride-rich lipoproteins correlate with the progression of early, preintrusive atherosclerosis of the carotid artery. These findings, together with earlier reports of the effects of lovastatin therapy on the progression of atherosclerosis of the coronary arteries, indicate that carotid arterial far wall intima-media thickness is a useful end point for anti-atherosclerosis trials.

Adult↗
PubMed1996

Plasma levels of lipoprotein (a) do not predict progression of human chronic renal failure.

Chronic renal failure is frequently accompanied by elevated plasma levels of lipoprotein (a) [Lp(a)]. Elevated Lp(a) levels have been proposed to contribute not only to increased risk of atherosclerotic and thrombotic complications but also to the progression of renal insufficiency. To investigate whether higher Lp(a) plasma concentrations are associated with an accelerated rate of progression of renal insufficiency, we have correlated baseline plasma concentrations of Lp(a) with the progressive decline of renal function in an observational study of human chronic renal disease. Forty-nine non-diabetic patients (40 men, nine women) were studied as part of an observational study of patients with moderately advanced renal insufficiency. The average follow-up time of the patient population was 3.1 years, and the mean rate of decline in glomerular filtration rate (51Cr-EDTA clearance) was -2.8 (SD 4.1) ml/min/1.73 m2. The mean plasma concentration of Lp(a) at the beginning of the study was 19.2 (SD 18.6) mg/100 ml with a median value of 12.2 mg/100 ml. There was no association between the initial plasma concentration of Lp(a) and the rate of progression as assessed by linear regression analysis. Furthermore, the progression rate in patients within the highest quartile of the Lp(a) distribution (> or = 30 mg/100 ml) did not differ from that in patients with lower levels of Lp(a). In contrast, increased levels of apolipoprotein (apo) B, low-density lipoprotein (LDL)-cholesterol, and proteinuria were all significantly associated with a more rapid decline in renal function. Based on these results, it was concluded that elevated plasma levels of Lp(a) are not associated with an increased rate of progression of renal insufficiency in human chronic renal disease. However, the results of this study suggest that other apoB-containing lipoproteins may play a significant role in this process.

Adult↗
PubMed1996

Diagnosis and classification of dyslipidemia in renal disease.

Renal disease is accompanied by specific alterations of the lipoprotein metabolism. While marked hyperlipidemia is a characteristic finding in the nephrotic syndrome, the dyslipoproteinemia of renal insufficiency is predominantly reflected in an abnormal apolipoprotein pattern but does not necessarily include elevated plasma lipid concentrations. The specific changes in nephrotic syndrome include increased formation primarily of cholesterol-rich and to a varying extent of triglyceride-rich ApoB-containing lipoproteins in the VLDL-LDL density range with little or no change among the ApoA-containing lipoproteins in HDL. The dyslipoproteinemia of renal failure is, on the other hand, mainly characterized by a decreased catabolism of the triglyceride-rich ApoB-containing lipoproteins with increased concentrations of partially metabolized lipoproteins of intermediate and very low density and a decreased concentration of ApoA-containing lipoproteins in HDL. In addition, increased levels of Lp(a) are found both in the nephrotic syndrome and in renal failure. Dialysis treatment appears to have only a modest influence on the renal dyslipoproteinemia. Due to its atherogenic character, the dyslipidemia of renal disease may be related to the accelerated development of cardiovascular disease in these patients.

Humans↗
PubMed1996

Abnormal lipid and apolipoprotein composition of major lipoprotein density classes in patients with chronic renal failure.

BACKGROUND AND METHODS: To characterize the abnormalities of lipoprotein composition in patients with chronic renal failure (CRF), the lipid and apolipoprotein (apo) concentrations and compositions of major lipoprotein density classes were determined in 20 subjects with moderate to advanced renal failure (GFR 5-59 ml/min) and nine controls. Patients were divided in 14 normotriglyceridaemic (NTG) subjects with triglyceride (TG) levels < or = 1.7 mmol/l (150 mg/dl) and six hypertriglyceridaemic (HTG) subjects with TG > or = 1.7 mmol/l. Lipoproteins were isolated by preparative ultracentrifugation: very low density (VLDL), intermediate density (IDL), low density (LDL) and high density (HDL) lipoproteins. RESULTS: Although all density classes were characterized by abnormal concentration and composition of some lipid and apo constituents, the most profound changes occurred in IDL and HDL. Cholesterol levels were elevated in VLDL and IDL with little change in LDL and reduced in HDL. TG levels were increased in all density classes. ApoB levels were increased in VLDL, IDL and LDL of all CRF patients reaching the significance levels in VLDL and IDL of HTG (P < 0.01). In IDL, the levels of apoC-peptides and apoE were increased (P < 0.01). ApoC-peptides and apo E were also elevated in VLDL of NTG and HTG, but their increase was only significant in HTG (P < 0.01). In LDL, the concentration of apoC-II and apoC-III was significantly increased (P < 0.05). However, in HDL there was significant (P < 0.01) reduction of apoA-I, apoA-II and apoC-peptides in both patient groups. The major compositional change was a significant increase in the relative contents of apoC-II and apoC-III in VLDL, IDL and LDL (P < 0.01). CONCLUSIONS: Results indicate that the characteristic feature of dyslipoproteinemia in CRF is the accumulation of partially delipidized TG-rich apoB-containing lipoproteins enriched in apoC-peptides and distributed characteristically in the IDL density-range irrespective of fasting TG concentrations. Increased levels of these ¿remnant lipoproteins' and reduced levels of HDL may represent risk factors for atherogenesis and progressive renal disease.

Adult↗
PubMed1996

Alterations in plasma lipoproteins and apolipoproteins before the age of 40 in heterozygotes for lipoprotein lipase deficiency.

We have assessed the expression of heterozygosity for lipoprotein lipase (LPL) deficiency by studying a single large French Canadian family comprising 92 persons including 21 carriers of the catalytically defective P207L mutation. Phenotypic changes distinguishing heterozygotes from controls were seen early, before the age of 40 and often before 20 years of age. In the total cohort these changes included an elevation in the mean very low density (VLDL) and intermediate density lipoprotein (IDL) triglyceride (+69%; P = 0.01 and +40%; P = 0.001) and cholesterol (+51%; P = 0.03 and +67%; P = 0.007) and apoB levels but decreased HDL2 and HDL3 cholesterol, (-32%; P = 0.01 and -15%; P = 0.002 respectively). While the lipid compositions of VLDL and IDL were similar between heterozygotes and controls, the low density (LDL) and high density lipoproteins (HDL) of carriers were triglyceride enriched. Heterozygotes also had a markedly lower apoC-III ratio (apoC-III in supernatant/apoC-III in heparin precipitate) (1.46 vs. 3.86 P = 1 x 10(-4)) indicating a substantial enrichment of VLDL and IDL with apoC-III and depletion of HDL apoC-III supporting this ratio as an effective index for efficiency of lipolysis. LpA-I was markedly reduced (0.34 vs. 0.43 P = 1 x 10(-5)) showing that levels of this particle are partly dependent on LPL catalytic activity. Heterozygotes manifest from an early age with a markedly reduced HDL, LpA-I, apoC-III ratio and an increased TC/HDLc ratio which would predict a relatively increased risk of premature coronary artery disease, compared to their normal siblings.

Adult↗
PubMed1995

Compensatory vascular changes of remote coronary segments in response to lesion progression as observed by sequential angiography from a controlled clinical trial.

BACKGROUND: Local coronary artery enlargement to compensate for atherosclerotic plaques preserves the vessel lumen. The extent to which coronary segments remote from progressing lesions enlarge is unknown. This is clinically relevant since compensatory enlargement may be important in determining whether clinical complications result from progression of coronary artery disease (CAD). Additionally, compensatory change has implications for quantitative coronary angiographic (QCA) trials, since the effect of progression on diameter means may be mitigated by compensatory changes in remote coronary segments when QCA change is averaged over all lesions. METHODS AND RESULTS: Serial QCA data from 78 subjects in the Monitored Atherosclerosis Regression Study were used to demonstrate compensatory changes in coronary segments remote from progressing or regressing lesions. Coronary segments were first classified as progressing (regressing) if percent diameter stenosis (PS) increased or decreased by > 10 with a concurrent decrease or increase in minimum lumen diameter (MLD) of either > 0.32 mm or > 10% of the normal baseline reference diameter (DNORM). Segments not meeting these criteria were labeled stenosis stable. Stenosis-stable segments opposite progressing lesions showed increases in MLD (P = .0006), DNORM (P = .001), and average diameter (P = .001). On-trial apolipoprotein (apo) B, apo C-III, and blood pressure levels inversely correlated with these compensatory changes. CONCLUSIONS: Lesion progression in one coronary segment is associated with significant increases in segmental diameter of remote parts of the coronary tree. We hypothesize these increases to be vascular compensatory changes in response to progression of CAD. Vascular compensatory change is enhanced by LDL cholesterol and triglyceride-rich lipoprotein reduction and appears to be part of the treatment effect itself.

Adult↗
PubMed1995

Changes in plasma lipid and apolipoprotein levels between heparin-induced extracorporeal low-density lipoprotein precipitation (HELP) treatments.

Heparin-induced extracorporeal low-density lipoprotein (LDL) precipitation (HELP) treatments selectively remove LDL with minimal effects on high-density lipoproteins (HDL), but limited data are available on effects between treatments. The levels of factors associated with increased coronary artery disease risk (atherogenic) among treatments may have therapeutic significance, especially for combined HELP and lipid-lowering drug therapy. Hypercholesterolemic and combined hyperlipidemic patients resistant to diet/drug therapy were treated with biweekly HELP therapy. Hypercholesterolemic patients received either lovastatin or no drug, whereas combined hyperlipidemic patients received gemfibrozil. Plasma lipid (total cholesterol, triglycerides, LDL cholesterol, and HDL cholesterol) and apolipoprotein A-I, A-II, B, C-III, and E levels were measured before treatment, then immediately, and 2, 4, 7, and 14 days after treatments (n = 28). Atherogenic factor (LDL cholesterol, total cholesterol, apolipoprotein B) levels decreased > 50% with treatment, gradually increasing over 14 days to pretreatment levels. Factors associated with reduced coronary artery disease risk (HDL cholesterol and apolipoproteins A-I and A-II) decreased 8% to 16% but recovered by 2 days. Components of triglyceride-rich lipoproteins (triglycerides and apolipoproteins C-III and E) decreased 38% to 55% with variable post-treatment recoveries. Lovastatin reduced pretreatment levels of atherogenic and triglyceride-rich lipoprotein components and slowed post-treatment increases compared with no drug therapy. Gemfibrozil produced changes similar to lovastatin. Drug therapy had little effect on factors associated with reduced coronary artery disease risk. HELP apheresis produced large reductions in plasma atherogenic factor levels with gradual return to pretreatment levels over 14 days, whereas antiatherogenic factors were minimally reduced and recovered rapidly.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Effects of lovastatin on ApoA- and ApoB-containing lipoproteins. Families in a subpopulation of patients participating in the Monitored Atherosclerosis Regression Study (MARS).

To establish whether lovastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, exhibits a specific effect on apolipoprotein (apo) A- and apoB-containing lipoproteins, 63 subjects, a subset of the 270 Monitored Atherosclerosis Regression Study (MARS) patients with hypercholesterolemia (190 to 295 mg/dL) and documented coronary artery disease, were randomized into either lovastatin 40 mg twice daily or matching placebo tablets twice daily. Both groups consumed a diet containing 27% calories as fat (polyunsaturated fat/saturated fat ratio, 2.85) and a daily cholesterol intake of less than 250 mg. The plasma lipid and apolipoprotein profiles were determined at the time of randomization and after 2 years of treatment, and the levels of apoA- and apoB-containing lipoprotein families were measured after 2 years of treatment. After this treatment period, the drug group was characterized in comparison with the placebo group by significantly reduced levels of total cholesterol (33%), triglycerides (30%), very-low-density lipoprotein cholesterol (36%), low-density lipoprotein cholesterol (43%), apoB (36%), apoC-III (18%), and apoE (17%) and slightly but insignificantly increased levels of high-density lipoprotein cholesterol (6%) and apoA-I (1%). The 2-year levels of lipoprotein containing apoA-I but no apoA-II (LpA-I) and lipoprotein containing both apoA-I and apoA-II (LpA-I/A-II) particles separated by immunoaffinity chromatography on an anti-apoA-II immunosorber did not differ between the two treatment groups. However, the apoB-containing lipoprotein (Lp) families defined by apolipoprotein composition and separated by immunoaffinity chromatography on anti-apoA-II and anti-apoC-III immunosorbers were affected in a selective manner.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Triglyceride- and cholesterol-rich lipoproteins have a differential effect on mild/moderate and severe lesion progression as assessed by quantitative coronary angiography in a controlled trial of lovastatin.

BACKGROUND: The Monitored Atherosclerosis Regression Study, a randomized, double-blind, placebo-controlled, 2-year trial of lovastatin monotherapy, found that coronary lesions < 50% diameter stenosis (%S) and coronary lesions > or = 50% S at baseline had different responses to therapy. We now report on clinical, lipid, and nonlipid risk factors of treatment response in these lesion subsets. METHODS AND RESULTS: Two hundred seventy subjects, 37 to 67 years old, with plasma total cholesterol (TC) 190 to 295 mg/dL (4.91 to 7.63 mmol/L) and total triglyceride < 500 mg/dL (5.65 mmol/L) were randomized to low-fat, low-cholesterol diet and either lovastatin 80 mg/d or placebo. Logistic regression was used to model the association between risk factors and coronary lesion progression in mild/moderate (< 50% S) and severe (> or = 50% S) lesions in 220 angiogram pairs analyzed by computer quantitative coronary angiography. In the placebo group, risk factors (P < .05) for the progression of mild/moderate lesions were triglycerides and TC/high-density lipoprotein cholesterol (HDL-C). Risk factors for the progression of severe lesions were HDL-C (negative), low-density lipoprotein cholesterol (LDL-C)/HDL-C, and TC/HDL-C. TC/HDL-C was the predominant risk factor for both mild/moderate and severe lesions in the multivariate analysis. In the lovastatin group, with aggressive lowering of LDL-C and TC below 85 mg/dL and 156 mg/dL, respectively, risk factors for mild/moderate lesions included triglycerides and very-low-density lipoprotein-LDL-associated apolipoprotein C-III (apo C-III-heparin precipitate), a marker of triglyceride-rich lipoprotein particles. Apo C-III-heparin precipitate was the predominant risk factor in the multivariate analysis. Risk factors for severe lesions were LDL-C, LDL-C/HDL-C, TC/HDL-C, and apo B; LDL-C/HDL-C was the predominant risk factor. CONCLUSIONS: These results indicate that triglyceride-rich lipoproteins and cholesterol-rich lipoproteins have a differential effect on mild/moderate and severe lesion progression, respectively. These results add to the growing evidence of the importance of triglyceride-rich lipoproteins as a risk factor for coronary artery disease and the need for treatment in the progression of atherosclerosis.

Adult↗
PubMed1994

Lipoprotein abnormalities without hyperlipidaemia in moderate renal insufficiency.

To characterize lipoprotein metabolism during early renal insufficiency, plasma lipid and apolipoprotein profiles were determined in normotriglyceridaemic (NTG, n = 31) and hypertriglyceridaemic (HTG, n = 30) middle-aged patients with primary renal disease and with moderately impaired renal function (GFR 20-55 ml/min, mean: 37.2). Mean GFR was similar in the two patient groups. They were compared with 102 normolipidaemic control subjects. In comparison with controls the NTG patients (plasma triglycerides TG < or = 1.7 mmol/l, mean TG: 1.16 mmol/l) had significantly increased plasma concentrations of apo C-III and apoB. The apoA-I levels tended to be lower and as a consequence the apoA-I/apoC-III ratio, considered to represent the hallmark of the altered apolipoprotein profile in renal dyslipoproteinaemia, was markedly lower in NTG patients (8.7 versus 16.8, P < 0.001). There was also a reduction of the antiatherogenic ratio apoA-I/apoB and an increase of the apoC-III/apoE ratio. The HTG patients (mean TG: 3.22 mmol/l) showed the same, but even more accentuated, qualitative changes as the NTG patients. There was a fourfold increase of apoC-III in VLDL-LDL lipoprotein fractions with little change in HDL in the HTG patients. In NTG patients the increase of apoC-III was found in VLDL-LDL and in HDL. Plasma insulin and PTH levels both correlated with the apoA-I/apoC-III ratio independently of GFR and BMI. This suggests a pathogenetic relationship between PTH-mediated alterations of insulin metabolism and the lipoprotein abnormalities.(ABSTRACT TRUNCATED AT 250 WORDS)

Apolipoproteins↗
PubMed1993

Coronary angiographic changes with lovastatin therapy. The Monitored Atherosclerosis Regression Study (MARS).

OBJECTIVE: To assess the effects of lipid-lowering therapy with lovastatin on coronary angiographic findings in patients with coronary artery disease and to compare the findings with those of two lipid-lowering angiographic trials using similar end points. DESIGN: Randomized, double-blind, placebo-controlled, multicenter coronary angiographic trial. SETTING: Community- and university-based cardiac catheterization laboratories. PARTICIPANTS: A total of 270 patients, 37 to 67 years old, with total cholesterol ranging from 4.92 to 7.64 mmol/L (190 to 295 mg/dL) and angiographically defined coronary artery disease. INTERVENTION: A cholesterol-lowering diet and either lovastatin, 80 mg/day, or placebo. OUTCOME: Per-patient change in percent diameter stenosis as determined by quantitative coronary angiography (primary end point). Global change score, based on the consensus of blinded expert readers regarding angiographic change (secondary endpoint). RESULTS: Lovastatin lowered total cholesterol level by 32%, low-density lipoprotein cholesterol by 38%, and the apolipoprotein B by 26% and raised the high-density lipoprotein cholesterol by 8.5% (P < 0.001). Average percent diameter stenosis increased 2.2% in placebo recipients and 1.6% in lovastatin recipients (P > 0.20). For lesions 50% or greater, average percent diameter stenosis increased 0.9% in placebo recipients and decreased 4.1% in lovastatin recipients (P = 0.005). The mean global change score was +0.9 (indicating progression) in the placebo group and +0.4 in the lovastatin group (P = 0.002); 13 placebo recipients and 28 lovastatin recipients had global change scores indicating regression (P < 0.02). CONCLUSION: Treatment with lovastatin plus diet slows the rate of progression and increases the frequency of regression in coronary artery lesions (by global change score), especially in more severe lesions (by quantitative angiography). This is the third lipid-lowering trial to show a benefit using the global change score, an end point predictive of clinical coronary events. Differences between two of these trials, using quantitative coronary angiographic end points, may have theoretical bearing on the mechanisms by which lipid-lowering therapy operates at the level of the arterial wall.

Adult↗
PubMed1993

Lipoprotein metabolism and renal failure.

Lipoprotein metabolism is altered in the majority of patients with renal insufficiency and renal-failure, but may not necessarily lead to hyperlipidemia. The dyslipoproteinemia of renal disease has characteristic abnormalities of the apolipoprotein (apo) profile and lipoprotein composition. It develops during the asymptomatic stages of renal insufficiency and becomes more pronounced as renal failure advances. The qualitative characteristics of renal dyslipoproteinemia are not modified substantially by dialysis treatment. Patients with chronic renal disease may therefore be exposed to dyslipoproteinemia for long periods of time. The characteristic plasma lipid abnormality is a moderate hypertriglyceridemia. The alterations of lipoprotein metabolism affect both the apoB-containing very low-density and intermediate-density, and low-density lipoproteins and the apoA-containing high-density lipoproteins. The main underlying abnormality of lipoprotein transport is a decreased catabolism of the apoB-containing lipoproteins caused by decreased activity of lipolytic enzymes and altered lipoprotein composition. There is an increase of intact or partially metabolized, triglyceride-rich, apoB-containing lipoproteins with a disproportionate elevation of apoC-III and, to a lesser extent, apoE, resulting in a marked increase of the intermediate-density lipoproteins and an enrichment of triglycerides, apoC-III, and apoE in the low-density lipoproteins. In high-density lipoproteins there are decreases in the concentrations of cholesterol, apolipoproteins A-I and A-II, and the high-density lipoprotein-2 to high-density lipoprotein-3 ratio. These abnormalities result in a characteristic decrease of the apoA-I to apoC-III ratio and anti-atherogenic index apoA-I/apoB. The pathophysiologic links between the renal insufficiency and the abnormalities of lipoprotein transport are still poorly defined. Changes in the action of insulin on lipolytic enzymes, possibly mediated via increased levels of parathyroid hormone, have been suggested to play a contributory role. The clinical consequences of a defective lipoprotein transport may be related to the atherogenic character of lipoprotein abnormalities. Renal dyslipoproteinemia may contribute to the development of atherosclerotic vascular disease and progression of glomerular and tubular lesions with subsequent deterioration of renal function. Dietary and/or pharmacologic intervention may ameliorate the uremic dyslipoproteinemia, but the long-term clinical effects of such treatment have yet to be established.

Apolipoproteins↗
PubMed1993

Apolipoprotein-B-containing lipoproteins and the progression of renal insufficiency.

Hyperlipidemia is associated with accelerated glomerular sclerosis in experimental renal insufficiency. To investigate whether the dyslipoproteinemia seen in human renal failure also influences the future course of renal insufficiency, we have correlated plasma levels of lipids and apolipoproteins at start of follow-up with the subsequent change in renal function in 34 adult patients with chronic renal disease. Nineteen patients had primary renal disease, and 15 patients had diabetic nephropathy. Except for antihypertensive therapy no specific treatment to modify the progression of the disease was given during the follow-up. The rate of progression was determined by repeated measurements of the glomerular filtration rate (GFR). The time of follow-up ranged from 12 to 91 months with an average of 39.7 +/- 16.7 months. The mean initial GFR was 34.7 +/- 13.9 ml/min x 1.73 m2 body surface area and the average decline in renal function was -0.27 +/- 0.26 ml/min/month. The entry levels of triglycerides (TG; p = 0.04), very-low-density lipoprotein cholesterol (p = 0.03), apolipoprotein-B (ApoB; p = 0.008) and systolic blood pressure (SBP; p = 0.04) were significantly correlated with the rate of progression. Among lipoprotein variables, ApoB showed the strongest correlation with the decline in GFR. Patients with a progressive course of their disease also tended to have initially higher levels of total cholesterol (TC) and low-density lipoprotein cholesterol (NS), whereas the initial plasma concentration of high-density lipoprotein cholesterol did not show an association with the progression of renal insufficiency.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗