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Lipoprotein and apolipoprotein profile in men with ischemic stroke. Role of lipoprotein(a), triglyceride-rich lipoproteins, and apolipoprotein E polymorphism.

Background and Purpose: The role of lipoprotein abnormalities in the development of ischemic cerebrovascular disease has not been sufficiently clarified. The aim of this study was to identify the lipoprotein profile in ischemic cerebrovascular disease and the possible role of apolipoprotein E polymorphism. Methods: The relation between the concentrations of lipoprotein(a), intermediate density lipoproteins, apolipoprotein A-I, apolipoprotein B, apolipoprotein E, and other lipoproteins was studied in 100 men with ischemic cerebrovascular disease (48 atherothrombotic, 28 lacunar, and 24 of unknown type) and in 100 healthy age-matched men as a control group. Results: Patients with ischemic cerebrovascular disease had significantly higher levels of lipoprotein (a), lipids carried by intermediate density lipoproteins, and low density lipoprotein cholesterol and lower levels of high density lipoproteins than control subjects. Patients with atherothrombotic infarction had higher total serum cholesterol and low density lipoprotein cholesterol concentrations than patients with lacunar infarction. To assess lipoprotein abnormalities in normolipidemic subjects, a subgroup of 38 patients with ischemic cerebrovascular disease and 53 control subjects, both with serum cholesterol levels <5.2 mmol/1 (200 mg/dl) and triglycerides <2.3 mmol/1 (200 mg/dl), was analyzed. Serum lipoprotein (a), lipids carried by very low density lipoproteins and intermediate density lipoproteins, and low density lipoprotein triglycerides were significantly higher in normolipidemic patients compared with normolipidemic control subjects, whereas high density lipoprotein cholesterol levels were lower. Apolipoprotein E polymorphism in our ischemic cerebrovascular patients differed from that of the control group, with the ϵ4 allele being more prevalent. Conclusions: Increased serum lipoprotein (a) levels and intermediate density lipoprotein abnormalities together with decreased high density lipoprotein levels are major risk factors for ischemic cerebrovascular disease, even in normocholesterolemic and normotriglyceridemic subjects. Finally, the ϵ4 allele could probably be a predisposing genetic marker for ischemic cerebrovascular disease.

Calculated Low-Density Lipoprotein Cholesterol Should Not Be Used for Management of Lipoprotein Abnormalities in Patients With Diabetes Mellitus

OBJECTIVE To assess the validity of calculated low-density lipoprotein cholesterol by the Friedewald formula for management of lipoprotein abnormalities in patients with diabetes mellitus. RESEARCH DESIGN AND METHODS Calculated LDL cholesterol by the Friedewald formula was compared with measured LDL cholesterol after separation by ultracentrifugation in 61 patients with type I diabetes, 50 patients with type II diabetes, and 116 healthy control subjects. RESULTS Calculated LDL cholesterol coincided with measured LDL cholesterol, with < 10% error, in 54 (49%) patients with diabetes mellitus, and 85 (73%) control subjects. Calculated LDL cholesterol was overestimated, with an error of > or = 10% of measured LDL cholesterol in 39% of patients and 26% of control subjects, and underestimated in 13 and 1%, respectively. Despite a good correlation between calculated and measured LDL cholesterol, the intraclass correlation coefficients demonstrated a poor concordance between calculated and measured LDL cholesterol, both in patients and control subjects. When comparing the mean differences of calculated and measured LDL cholesterol for diabetic subjects versus control subjects, significantly greater differences in type II (but not type I) diabetic subjects were seen. CONCLUSIONS Calculation of LDL cholesterol by the Friedewald formula may be inaccurate for assessment of cardiovascular risk in patients with type II diabetes and may not be appropriate for management of lipoprotein abnormalities in those diabetic patients.

Lipoprotein profile in men with peripheral vascular disease. Role of intermediate density lipoproteins and apoprotein E phenotypes.

BackgroundThe role of lipoprotein disturbances in the development of peripheral vascular disease (PVD) has not been sufficiently clarified. Methods and ResultsThe relations among concentrations of intermediate density lipoproteins (IDL), apoprotein (apo) B, apo E, and other lipoproteins were studied in 102 men with PVD and 100 healthy men who formed the control group. Patients with PVD had significantly higher levels of serum triglycerides, very low density lipoprotein (VLDL) cholesterol, VLDL triglycerides, VLDL proteins, IDL cholesterol, and IDL triglycerides and lower levels of high density lipoproteins (HDL) than controls. Serum cholesterol and triglycerides were normal in 30 patients (cholesterol, < 5.2 mmol/l; triglycerides, < 2.3 mmol/1), who had significant increases in IDL triglycerides and significant decreases in HDL cholesterol compared with the 47 controls, who had normal cholesterol and triglyceride levels. Patients with more severe distal involvement showed higher cholesterol and triglycerides carried by IDL and a greater reduction in HDL cholesterol. Smoking patients with PVD showed increased VLDL cholesterol and VLDL triglycerides and lower HDL concentrations. Apo E polymorphism in our study population does not differ from that reported for other European populations. Alleles ∈2 and ∈4 had a major impact on serum triglycerides and VLDL lipids in our patients with PVD ConclusionsLipoprotein disturbances are a major risk factor for PVD. IDL abnormalities play an important role in the development and severity of PVD and should also be considered a vascular risk factor in normocholesterolemic and normotriglyceridemic patients.

Apolipoprotein(a) genetic polymorphism and serum lipoprotein(a) concentration in patients with peripheral vascular disease

Serum lipoprotein(a) (Lp(a)) levels were measured in 89 men with peripheral vascular disease (PVD) and 129 (100 male and 29 woman) healthy controls. Apolipoprotein(a) genetic polymorphism was determined by immunoblotting in all subjects. Patients with PVD had significantly higher serum Lp(a) levels than controls. Apolipoprotein(a) phenotype frequencies in patients with PVD did not differ from those of the control group. Both patients and controls with phenotype S2 had higher serum Lp(a) levels than those with phenotype S4. It should be emphasized that serum Lp(a) levels were significantly higher in PVD patients than controls for those with phenotype S2, S3/S4 and S4. Raised serum Lp(a) levels together with other lipoprotein abnormalities in patients with PVD imply a high cardiovascular risk. Genetic polymorphism clearly influences serum Lp(a) levels both in patients and controls. In patients with PVD, environmental and/or other genetic factors must play a role in raising Lp(a) levels.

Relationship Between Lineprotein Profile and Urinary Albumin Excretion in Type II Diabetic Patients With Stable Metabolic Control

OBJECTIVE To assess lipids and lipoprotein composition and the relationship between lipoprotein abnormalities and urinary albumin excretion (UAE) in select type II diabetic patients with stable metabolic control. RESEARCH DESIGN AND METHODS Fifty-five type II diabetic patients and 55 healthy control subjects both with a body mass index <30 kg/m2 were studied. Patients were classified according to their level of UAE as normoalbuminuric (n = 37), microalbuminuric (n = 11), and macroalbuminuric (n = 7). In all cases, serum creatinine and albumin concentrations were in the normal range. RESULTS Normoalbuminuric patients showed increased triglyceride (TG) contents in intermediate-density lipoprotein (IDL) (P < 0.01), low-density lipoprotein (LDL) (P < 0.001), and high-density lipoprotein (HDL) (P < 0.001) compared with control subjects. Lipoprotein concentration in microalbuminuric patients did not differ from that of normoalbuminuric patients. On the other hand, patients with macroalbuminuria showed a significant increase in IDL cholesterol (P < 0.01) and IDL (P < 0.01), LDL (P < 0.05), and HDL TGs (P < 0.01) compared with the other groups. Diabetic patients with nephropathy, both microalbuminuric and macroalbuminuric, tended to have higher mean lipoprotein(a) (Lp[a]) concentrations than normoalbuminuric patients and control subjects. A strongly positive correlation was observed between UAE and serum TGs (r = 0.56) and very-low-density lipoprotein (r = 0.55), IDL (r = 0.52), LDL (r = 0.54), and HDL TGs (r = 0.52). CONCLUSIONS Lipoprotein alterations observed in diabetic patients, specifically IDL abnormalities and a tendency toward high Lp(a) levels, which are more marked in those with increased UAE, may contribute to the excess of cardiovascular disease in type II diabetic patients, particularly those with nephropathy.

When to treat dyslipidaemia of patients with chronic renal failure on haemodialysis? A need to define specific guidelines

BACKGROUND There are no specific recommendations for management of dyslipidaemia in patients with chronic renal failure (CRF) on haemodialysis, in which atherosclerosis is a common cause of morbidity and mortality. The aim of the present study was to analyse different approaches based on low-density lipoprotein (LDL) cholesterol (measured and calculated with a formula), non-high-density lipoprotein (HDL) cholesterol, and HDL cholesterol levels in the clinical management of dyslipidaemia in haemodialysis patients. METHODS Calculated LDL cholesterol by the Friedewald formula was compared with measured LDL cholesterol after separation by ultracentrifugation in 101 male patients with CRF on haemodialysis and in 101 healthy control subjects. RESULTS Calculated LDL cholesterol coincided with measured LDL cholesterol, with less than 10% error, in 54 patients (53.4%) and in 75 controls (74.2%). Calculated LDL cholesterol was overestimated, with an error of 10% or more with respect to measured LDL cholesterol, in 37.6% of patients and in 23.7% of controls, and underestimated in 8.9% and 1. 9% respectively. Despite a good correlation between calculated and measured LDL cholesterol, the intraclass correlation coefficients demonstrate a poor concordance between calculated and measured LDL cholesterol, both in patients and controls. Only 17 patients were at non-HDL cholesterol level risk defined as higher than 4.28 mmol/l. HDL cholesterol levels lower than 0.9 mmol/l were found in 70% of patients and in 23% of controls. CONCLUSIONS LDL or non-HDL cholesterol levels may not be appropriate for management of lipoprotein abnormalities in CRF patients. Further studies must clarify whether HDL cholesterol may be the best lipoprotein parameter for evaluating cardiovascular risk in these patients.

Lipoprotein composition in the insulin-deficient non-acidotic phase of type I diabetic patients and early evolution after the start of insulin therapy

Lipoproteins, including intermediate density lipoproteins and lipoprotein(a), and apolipoproteins A-I, B, C-II, C-III and E, were studied in 13 newly-diagnosed type I diabetic patients with severe insulinopenia without dehydration or acidosis. At baseline, the main finding was a significant increase in serum triglycerides due to raised triglyceride concentrations in all lipoproteins, particularly triglyceride-rich lipoproteins. Cholesterol concentrations were slightly increased in lipoproteins and led to a significant increase in serum cholesterol. Two days after the start of insulin therapy, lipoprotein profiles had normalized except for the LDL triglyceride contents, which remained significantly increased on the fifth day of treatment. No significant modifications were observed in lipoprotein(a), apolipoproteins A-I and E concentrations throughout the study. However, serum apolipoproteins B, C-II and C-III were increased at baseline and fell to normal levels 2 days after the start of insulin therapy. On the other hand, apolipoprotein C-II/C-III ratios in high and very low density lipoprotein, showed no significant differences at baseline compared with controls, suggesting that an apolipoprotein C-II deficiency or apolipoproteins Cs imbalance can be ruled out. In conclusion, significant lipoprotein abnormalities were observed in the insulin-deficient state of type I diabetes mellitus; insulin therapy normalizes the lipoprotein profile in two days, except for low density lipoprotein triglyceride contents which remain increased at the fifth day.

Influence of Apolipoprotein(a) Genetic Polymorphism on Serum Lipoprotein(a) Concentration in Patients with Ischemic Cerebrovascular Disease

Increased serum lipoprotein(a) levels are an independent risk factor for ischemic cerebrovascular disease, even in normocholesterolemic and normotri-glyceridemic subjects. The aim of the present study

Secondary prevention of coronary heart disease in patients with extracoronary atherosclerosis: a need for accuracy of low density lipoprotein determination.

According to the new guidelines of the National Cholesterol Education Program (NCEP) for secondary prevention in adults with evidence of coronary heart disease or other clinical atherosclerotic disease, lipoprotein analysis is required and classification is based on low density lipoprotein (LDL) cholesterol. The aim of the present study was to analyze the reliability of calculated LDL cholesterol by the Friedewald formula compared with measured LDL cholesterol after separation by ultracentrifugation in 202 male patients with extracoronary atherosclerosis (100 patients with ischemic cerebrovascular disease and 102 patients with peripheral vascular disease) and in 117 healthy control subjects. Calculated LDL cholesterol coincided with measured LDL cholesterol, with less than 10% error, in 118 patients (58.4%) with extracoronary atherosclerosis and in 87 controls (74.4%). Calculated LDL cholesterol was overestimated, with an error of 10% or more compared with measured LDL cholesterol, in 34.6% of patients and 22.2% of controls, and underestimated in 6.9% and 3.4%, respectively. Despite a good correlation between calculated and measured LDL cholesterol, the intraclass correlation coefficients demonstrate a poor concordance between calculated and measured LDL cholesterol, both in patients and controls. The authors underline the need for caution in assessing the reliability of calculated LDL cholesterol.