Evaluation of dyslipidaemia in patients with rheumatoid arthritis in South Indian population

BackgroundRheumatoid arthritis (RA) is associated with increased cardiovascular morbidity and mortality which is mainly due to accelerated atherosclerosis. The inflammation in rheumatoid arthritis is likely to alter the lipid profile in these patients resulting in dyslipidaemia which is an important cardiovascular disease (CVD) risk factor.Material and methods46 patients diagnosed with RA as per 1987 revised American Rheumatology Association criteria were included in the study. Of the 46 patients, 24 were newly diagnosed RA patients and 22 patients were undergoing treatment with a combination of DMARDs with (n = 14) or without (n = 8) corticosteroids. 46 age and sex matched healthy subjects were included as controls. Total cholesterol (TC), triglycerides, HDL cholesterol, lDL cholesterol, apolipoprotein A-1 (apo A-1), apolipoprotein B (apo B) and lipoprotein(a) (Lp(a)) were measured.ResultsTC, HDL cholesterol and LDL cholesterol levels were similar in all the three study groups. Both groups of patients had significantly elevated triglyceride, apo B and Lp(a) levels compared to controls (p < 0.05). RA patients undergoing treatment had significantly elevated apo A-1 levels when compared to controls (p < 0.05).ConclusionsThe dyslipidaemia pattern in RA patients in the present study is evident in the form of elevated triglycerides, apo B and Lp(a) levels. The beneficial effects of a higher atheroprotective apo A-1 in patients undergoing treatment may be counteracted by the presence of high triglycerides, apo B and Lp(a).     

Serum lipoprotein (a) levels in men with peripheral vascular disease.

The authors quantified serum lipoprotein (a) (Lp) (a) by enzymo-immuno-analysis in 86 outpatient men suffering peripheral vascular disease (PVD) and in 53 age-matched healthy men. They further measured serum cholesterol, serum triglycerides, low density lipoproteins-cholesterol, high density lipoproteins (HDL)-cholesterol and serum apolipoprotein B. Serum triglycerides were significantly increased in patients with PVD versus controls (148 +/- 8 and 114 +/- 7 mg/dL, mean +/- SEM). HDL-cholesterol levels were significantly lower in patients versus controls (36 +/- 1 and 43 +/- 2 mg/dL, respectively). Serum Lp(a) levels in patients with PVD were 20 +/- 2 mg/dL, whereas in controls they were 16 +/- 3 (p: NS). Serum Lp(a) concentrations were identical in smoker and nonsmoker patients. There was no correlation between Lp(a) concentration and the other lipid parameters. Conversely, as occurs in coronary heart disease and in cerebrovascular disease, Lp(a) does not seem to be a marker for PVD, although a trend toward a higher mean levels was found.     

Plasma lipoprotein (a) levels in Turkish NIDDM patients with and without vascular diabetic complications.

OBJECTIVE: Plasma concentrations of lipoprotein (a) [Lp(a)], an independent risk factor for atherosclerosis, were measured in 59 non-insulin-dependent diabetes mellitus (NIDDM) patients with and without vascular complications, and 21 non-diabetic healthy subjects. RESULTS: The plasma log Lp(a) levels were found to be significantly increased in the NIDDM patients (1.40 +/- 0.36) compared with the healthy subjects (1.02 +/- 0.53; p < 0.05). Plasma Lp(a) levels in NIDDM patients with diabetic vascular complications (1.51 +/- 0.27) were significantly higher than those of the NIDDM patients without diabetic vascular complications (1.23 +/- 0.43) and healthy subjects (p < 0.05). There were significant correlations between plasma log Lp(a) levels and apolipoprotein B (apo B) in all NIDDM patients (r: 0.68, p < 0.05). No correlation was observed between Lp(a) levels and age, sex, duration of diabetes, fasting blood glucose, haemoglobin Alc, the mode of treatment, triglycerides, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and apolipoprotein Al levels in all patients. CONCLUSIONS: It was concluded that Lp(a) was a risk factor for angiopathy in NIDDM patients and the patients who have a high plasma Lp(a) concentration should be kept under strict glycaemic control.     

Lipoprotein cholesterol, apolipoprotein A-I and B and lipoprotein (a) abnormalities in men with premature coronary artery disease.

The prevalence of abnormalities of lipoprotein cholesterol and apolipoproteins A-I and B and lipoprotein (a) [Lp(a)] was determined in 321 men (mean age 50 +/- 7 years) with angiographically documented coronary artery disease and compared with that in 901 control subjects from the Framingham Offspring Study (mean age 49 +/- 6 years) who were clinically free of coronary artery disease. After correction for sampling in hospital, beta-adrenergic medication use and effects of diet, patients had significantly higher cholesterol levels (224 +/- 53 vs. 214 +/- 36 mg/dl), triglycerides (189 +/- 95 vs. 141 +/- 104 mg/dl), low density lipoprotein (LDL) cholesterol (156 +/- 51 vs. 138 +/- 33 mg/dl), apolipoprotein B (131 +/- 37 vs. 108 +/- 33 mg/dl) and Lp(a) levels (19.9 +/- 19 vs. 14.9 +/- 17.5 mg/dl). They also had significantly lower high density lipoprotein (HDL) cholesterol (36 +/- 11 vs. 45 +/- 12 mg/dl) and apolipoprotein A-I levels (114 +/- 26 vs. 136 +/- 32 mg/dl) (all p less than 0.005). On the basis of Lipid Research Clinic 90th percentile values for triglycerides and LDL cholesterol and 10th percentile values for HDL cholesterol, the most frequent dyslipidemias were low HDL cholesterol alone (19.3% vs. 4.4%), elevated LDL cholesterol (12.1% vs. 9%), hypertriglyceridemia with low HDL cholesterol (9.7% vs. 4.2%), hypertriglyceridemia and elevated LDL cholesterol with low HDL cholesterol (3.4% vs. 0.2%) and Lp(a) excess (15.8% vs. 10%) in patients versus control subjects, respectively (p less than 0.05). Stepwise discriminant analysis indicates that smoking, hypertension, decreased apolipoprotein A-I, increased apolipoprotein B, increased Lp(a) and diabetes are all significant (p less than 0.05) factors in descending order of importance in distinguishing patients with coronary artery disease from normal control subjects. Not applying a correction for beta-adrenergic blocking agents, sampling bias and diet effects leads to a serious underestimation of the prevalence of LDL abnormalities and an overestimation of HDL abnormalities in patients with coronary artery disease. However, 35% of patients had a total cholesterol level less than 200 mg/dl after correction; of those patients, 73% had an HDL cholesterol level less than 35 mg/dl.     

Current standards in diagnosis and therapy of hyperlipoproteinemia

Raised lipid parameters, especially increased LDL-cholesterol and lipoprotein(a) (Lp(a)) levels, are severe risk factors for atherosclerosis. Targets in the therapy of hyperlipoproteinemia are dependent on other risk factors including diabetes mellitus and manifest cardiovascular disease. Fasting levels of total cholesterol, LDL-cholesterol, HDL-cholesterol, and triglycerides are measured for diagnosis of this disease. Lp(a) should be evaluated in instances of positive family history for cardiovascular disease and/or severe progress of cardiovascular disease or premature cardiovascular events. The basis of therapy includes diet measures as well as weight reduction and lifestyle modifications (raised physical activity after excluding contraindications). Numerous patients require lipid-lowering drug therapy, including most importantly statins but also bile acid sequestrants, ezetimibe, fibrates, nicotinic acid or omega-3-fatty acids. Special forms of hyperlipoproteinemia such as chylomicronemia syndrome and raised Lp(a) are described herein.     

Chylomicron metabolism is markedly altered in systemic lupus erythematosus

OBJECTIVE: To verify the in vivo status of chylomicron metabolism in systemic lupus erythematosus (SLE) since there is a high incidence of atherosclerosis in this disease and chylomicrons may have an important role in atherogenesis. METHODS: A chylomicron-like emulsion labeled with 14C-cholesteryl esters and 3H-triglycerides was injected intravenously into 10 female patients with inactive SLE and 10 healthy age- and sex-matched control subjects to determine the plasma kinetics of the emulsion lipids from consecutive plasma samples taken at regular intervals for 1 hour. Lipolytic activity was determined in vitro after incubation of the labeled emulsion with postheparin plasma. RESULTS: The decay curves for the emulsion were markedly slowed in SLE. Chylomicron lipolysis, indicated by the fractional clearance rate (FCR) of emulsion 3H-triglyceride, was 2-fold smaller in SLE patients than in controls (mean +/- SD 0.023 +/- 0.011 versus 0.047 +/-0.015 minute(-1); P = 0.010). Chylomicron removal, indicated by emulsion 14C-cholesteryl ester FCR, was 3-fold smaller in SLE patients than in controls (0.007 +/-0.007 versus 0.023 +/- 0.011 minute(-1); P = 0.009). In vitro lipolysis in SLE patients was nearly half that of the controls (mean +/- SD 10,199 +/- 2,959 versus 6,598 +/-2,215; P = 0.014). Higher levels of very-low-density lipoprotein cholesterol and triglycerides and lower levels of high-density lipoprotein cholesterol and apolipoprotein A-I were also observed in the SLE patients. CONCLUSION: SLE patients have disturbances in chylomicron metabolism that are characterized by decreased lipolysis and chylomicron remnant removal from the plasma. This finding, together with other alterations in lipid profiles that were confirmed in the present study, is largely accountable for the accelerated atherosclerotic process of the disease.     

Nephrotic-range proteinuria, the major risk factor for early atherosclerosis in juvenile-onset systemic lupus erythematosus

OBJECTIVE: To determine the presence of early carotid atherosclerosis and associated risk factors in patients with juvenile-onset systemic lupus erythematosus (SLE). METHODS: The carotid intima-media wall thickness (IMT) was measured by B-mode ultrasound in patients with SLE onset before the age of 16 years and in sex- and age-matched healthy control subjects. Risk factors for atherosclerosis were determined at the time of the ultrasound scan and included traditional cardiovascular and SLE-related risk factors. RESULTS: Twenty-six patients with juvenile-onset SLE and 26 healthy controls were studied. The mean (+/- SD) IMT of the SLE patients was significantly higher than that of the control group (0.57+/-0.05 mm and 0.54+/-0.03 mm, respectively; P = 0.006). The results of IMT measurement were not correlated with the patients' age, disease duration, SLE Disease Activity Index (SLEDAI) score, Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index (DI) score, laboratory indicators of lupus activity, or cumulative prednisone dose. Patients with nephrotic-range (NR) proteinuria (> or = 3.5 gm/24 hours; n = 6) had a significantly higher IMT than did those without (n = 20) (P = 0.02). Patients with NR proteinuria also had significantly higher SLEDAI scores, SLICC/ACR DI scores, and systolic and diastolic blood pressures, and significantly higher levels of total cholesterol, low-density lipoprotein cholesterol, apolipoprotein B, and fibrinogen. No difference in any of the above variables, including the IMT, was observed when SLE patients without NR proteinuria were compared with healthy controls. CONCLUSION: These patients with juvenile-onset SLE had ultrasonographic evidence of premature atherosclerosis. The risk of early atherosclerosis may be higher in patients with NR proteinuria.     

Prevalence of lipoprotein (a) [Lp(a)] excess in coronary artery disease

Lipoprotein (a) [Lp(a)] is composed of 1 low-density lipoprotein (LDL) particle, to which 1 molecule of apolipoprotein (a) is covalently linked. Elevated levels of Lp(a) have been associated with coronary artery disease (CAD) and Lp(a) has been shown to be highly heritable. Our purpose was to determine the prevalence of familial Lp(a) excess in patients with CAD. We determined plasma levels of Lp(a) in 180 patients (150 men and 30 women) with angiographically documented CAD before age 60 years, and in 459 control subjects (276 men and 183 women) clinically free of cardiovascular disease. In addition, Lp(a) levels were determined in families of 102 of the CAD probands (87 men and 15 women). No gender differences in Lp(a) levels were observed between men and women (patients or control subjects). Patients with CAD had higher Lp(a) levels than did control subjects (19 +/- 21 vs 13 +/- 15 mg/dl, p less than 0.001). The prevalence of Lp(a) excess (defined as greater than 90th percentile of controls) was 17% in patients with CAD (p less than 0.05). Lp(a) levels were not correlated with cholesterol, LDL cholesterol, high-density lipoprotein (HDL) cholesterol or apolipoproteins A-I or B. There was a weak correlation between Lp(a) and triglycerides (r = 0.166, p less than 0.05) in patients and control subjects. Stepwise discriminant analysis revealed that Lp(a) was a risk factor for the presence of CAD in men, independent of smoking, hypertension, diabetes, LDL and HDL cholesterol, or apolipoprotein A-I and B levels. Family studies revealed that Lp(a) levels are strongly genetically determined.(ABSTRACT TRUNCATED AT 250 WORDS)     

Serum lipids and lipoproteins in type 2 diabetic patients with persistent microalbuminuria

To investigate whether persistent microalbuminuria is related to altered levels of both lipids and apolipoproteins in Type 2 diabetes mellitus serum total-cholesterol, triglycerides, HDL-cholesterol, LDL-cholesterol, apolipoprotein A-I, and apolipoprotein B were measured by standard methods in a group of Type 2 diabetic patients affected by persistent microalbuminuria (albumin excretion rate (AER) 20-200 micrograms min-1) as compared with a group of sex- and age-matched non-microalbuminuric patients (AER less than 20 micrograms min-1). The groups were stratified according to a short (less than or equal to 5 years) or a longer (greater than 5 years) duration of diagnosed diabetes. Microalbuminuria was not associated with significant changes of serum total-cholesterol, triglycerides, HDL-cholesterol, LDL-cholesterol, and apolipoproteins in the group of patients with a duration of disease greater than 5 years, while microalbuminuric patients less than or equal to 5 years from diagnosis (n = 11) had serum total-cholesterol, triglycerides, LDL-cholesterol, and apoprotein B higher than non-microalbuminuric control patients (n = 26) (cholesterol 6.2 +/- 0.9 vs 5.1 +/- 1.0 mmol l-1 (p = 0.003); triglycerides 2.1 +/- 0.7 vs 1.7 +/- 1.3 mmol l-1 (p = 0.03); LDL-cholesterol 4.1 +/- 0.8 vs 3.0 +/- 0.7 mmol l-1 (p less than 0.001); apo-B 1.3 +/- 0.3 vs 1.1 +/- 0.3 g l-1 (p = 0.02). In these patients with shorter duration of diabetes many of the serum lipid measures correlated positively with AER.     

Lipid profiles in untreated patients with rheumatoid arthritis.

OBJECTIVE: To investigate lipid profiles in patients with untreated active rheumatoid arthritis (RA) and to assess the relationship of the inflammatory condition of RA with lipid profiles. METHODS: Forty-two patients with RA and 42 age and sex matched healthy controls were studied. Patients with RA had not been treated with corticosteroid or disease modifying antirheumatic drugs prior to the study. Total cholesterol, triglyceride, HDL-cholesterol, LDL-cholesterol, apolipoprotein A1 (apo A1), apolipoprotein B (apo B), lipoprotein(a) [Lp(a)], and C-reactive protein (CRP) were measured in both groups. RESULTS: The levels of apo A1 and HDL-cholesterol were significantly lower in patients than in controls (128.5 vs. 151.8 mg/dl, 41.2 vs. 54.9 mg/dl, respectively). The level of Lp(a) was significantly higher in patients than in controls (27.1 vs. 18.0 mg/dl). The ratios of apo B/apo A1, total cholesterol/HDL-cholesterol, and LDL-cholesterol/HDL-cholesterol were significantly higher in patients than in controls (0.82 vs. 0.67, 4.4 vs. 3.4, 2.8 vs. 1.9, respectively). CRP showed a significant correlation with apo A1 (r = -0.44, p<0.01) and HDL-cholesterol (r = -0.35, p<0.05). CONCLUSION: Our study suggests that patients with untreated active RA have altered lipoprotein and apolipoprotein patterns that may possibly expose them to higher risk of atherosclerosis. The inflammatory condition of RA may affect the metabolism of HDL-cholesterol and apo A1.     

Assessment of metabolic atherosclerosis risk factors in progeny of patients with past ischemic stroke

Early diagnosing and modification or elimination of atherosclerosis risk factors with the descendants of the ill with past ischemic stroke (IS) might reduce risk of subsequent stroke incidence in the family, or myocardial infarction or other disease being atherosclerosis - derivative. This subject seems to be essential because it concerns young people. The purpose of the present study is identification and assessment of metabolic atherosclerosis risk factors with adult progeny of the ill with past IS at young age. There were examined 43 adult children of the parents who fell ill at young age (between 39 and 55 years in case of men and 60 years in case of women) with IS. The test group included 21 men and 22 women aged from 19 to 39 years (average age - 26.3 years). The reference group consisted of 40 persons, including 18 men and 22 women aged from 22 to 39 years (average age - 26.8 years). The persons from reference group were corresponding (in respect of structural aspects, such as age and sex) to the test group, their parents had negative history towards atherosclerosis - derivative illnesses. None of the patients under examination was a cigarette smoker. Examination of both groups consisted in conducting anamnesis, measurement of body weighing and height, blood pressure as well as evaluation of biochemical atherosclerosis risk factors. Blood testing (blood serum or plasma) consisted of blood cell count and ESR as well as blood glucose level, creatinine, urea, transaminase and bilirubin levels as well as total cholesterol, LDL cholesterol and HDL cholesterol fractions, apolipoprotein B, apolipoprotein AI, lipoprotein (a), triglycerides, homocysteine, folate, fibrinogen, von Willebrand factor and C-reactive protein level. Among persons whose parents were affected, at young age, with IS higher average level of BMI (24.2 +/- 3.8 kg/m2) was detected as compared with that in the reference group (22.4 +/- 2.5 kg/m2), LDL cholesterol fraction (2.7 +/- 0.8 mmol/l vs 2.4 +/- 0.6 mmol/l) and triglycerides (1.1 +/- 0.4 mmol/l vs 0.8 +/- 0.4 mmol/l) as well as lower level of apolipoprotein Al (1.5 +/- 0.2 g/l vs 1.6 +/- 0.2 g/l). Average values of other factors in the blood serum were not significantly different in both with compared groups. In case of women, whose parents were affected with IS, higher levels of the following indicators were detected: BMI (24.3 +/- 3.9 kg/mz vs 21.5 +/- 2.3 kg/m2), total cholesterol (5.1 +/- 0.7 mmol/l vs 4.4 +/- 0.5 mmol/l, LDL cholesterol (2.7 +/- 0.6 mmol/l vs 2.1 +/- 0.4 mmol/l), apolipoprotein B (1.0 +/- 0.1 g/l vs 0.8 +/- 0.1 g/l), lipoprotein (a) (0.3 +/- 0.2 g/l vs 0.2 +/- 0.1 g/l) and triglycerides (1.0 +/- 0.4 mmol/l vs 0.7 +/- 0.2 mmol/l). In group of men whose parents were affected with IS lower levels of apolipoprotein Al (1.3 +/- 0.2 g/l vs 1.5 +/- 0.2 g/l) and of von Willebrand factor (71.4 +/- 23.9% vs 87.1% +/- 16,8%) were detected. Descendents of the ill with past IS should be treated as higher risk group especially when supranormative values of metabolic atherosclerosis risk factors are detected with them. In case of persons with positive family history of IS, having higher values of metabolic atherosclerosis risk factors, it is necessary to apply intensive actions towards change of their life styles, and if necessary - also to include pharmacological treatment.     

Hydroxychloroquine has no significant effect on lipids and apolipoproteins in Chinese systemic lupus erythematosus patients with mild or inactive disease

OBJECTIVE: To investigate the effects of hydroxychloroquine (HCQ) in Chinese patients with systemic lupus erythematosus who were either on a low dose of prednisone or not on prednisone. METHODS: 65 consecutive Chinese lupus patients without features of nephritis underwent assessment of the fasting serum lipid profile, including total cholesterol (TC), triglycerides (TG), HDL-cholesteorl (HDL-C), LDL-cholesterol (LDL-C), apolipoprotein A-1 (apo A-1), apolipoprotein B (apo B) and lipoprotein (a) (Lp(a)). RESULTS: 44/65 (67.7%) patients were on HCQ with a dose of 244 +/- 86 mg daily and 34/65 (52.3%) patients were on 4.3 +/- 2.6 mg daily of prednisone. The percentages of patients taking prednisone and the mean dose in those patients receiving this treatment were not different between the groups with or without HCQ treatment. TG tended to be lower in those patients on HCQ (median and interquartile range) (1.0 (0.7-1.4) mmol/L vs 1.2 (0.8 1.6) mmol/L), but there were no significant differences in TC or other lipid parameters including Lp(a) between the 2 groups of patients with or without HCQ treatment. CONCLUSION: HCQ had no significant effect on the serum lipid profile in these lupus patients with mild or inactive disease. This finding probably reflects the low doses of corticosteroid used and a lower background lipid level in this population.     

Preclinical vascular disease in systemic lupus erythematosus and primary antiphospholipid syndrome

OBJECTIVE: To determine the prevalence of preclinical vascular disease and associated risk factors in patients with systemic lupus erythematosus (SLE) or primary antiphospholipid syndrome (APS). METHODS: We consecutively studied 70 SLE patients and 25 primary APS patients without clinical coronary artery disease. The control group included 40 healthy women. Carotid ultrasound was performed and the intima-media wall thickness (IMT) and presence of plaque was investigated in all patients and controls. Traditional vascular risk factors and SLE-disease and treatment related factors were also analysed. RESULTS: SLE patients had a higher prevalence of traditional atherosclerosis risk factors: hypertension (P<0.005) and dyslipidaemia (P<0.05) and higher levels of total cholesterol (P = 0.03), triglycerides (P = 0.004) and apolipoprotein B (P = 0.04). The prevalence of carotid plaque was higher and appeared earlier in SLE patients than in the primary APS patients or controls (P<0.001). The IMT was similar in the three groups. SLE patients with secondary APS had a higher prevalence of carotid plaque than patients with primary APS (37.5% vs 8%, P = 0.03). The presence of plaque in SLE patients was associated with a higher SLICC score (2.40 +/- 1.78 vs 1.02 +/- 1.18, P = 0.002), higher ECLAM score (3.10 +/- 2.32 vs 1.84 +/- 1.59, P = 0.02) and older age (47.3 +/- 8.44 vs 37.38 +/- 11.28, P = 0.003) at the time of carotid ultrasound study. CONCLUSION: Plaque prevalence in patients with primary APS is similar to that of controls and inferior to that of SLE patients with secondary APS. SLE patients have a high prevalence of early carotid atherosclerosis that is associated with cumulative disease damage and disease activity.     

Low order correlations of lipoprotein(a) with other blood lipids and with coagulation and fibrinolysis parameters in hypertensive and diabetic patients.

Lipoprotein(a) (Lp(a)) has been established as an important independent risk factor for the development of cardiovascular disease. Apolipoprotein(a), together with apo B-100 the apolipoprotein of Lp(a), is homologeous to plasminogen but lacks fibrinolytic capacity and appeared to interfere with fibrinolysis in in vitro and ex vivo experiments. We determined the correlations between Lp(a) and other blood lipids (serum cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides), coagulation parameters (fibrinogen, factor VII, factor VIII:C fibrin monomers, thrombin-antithrombin III) and fibrinolysis parameters (tissue plasminogen activator antigen, plasminogen activator inhibitor-1 and D-dimer) in 54 patients with essential hypertension, in 65 non-insulin-dependent diabetic patients and in 116 insulin-regulated diabetic patients. Signs of activated coagulation and increased reactive fibrinolysis were found in all three patient groups. In the hypertensive patients, Lp(a) was significantly correlated with LDL-cholesterol (r = 0.25, P = 0.04) and triglycerides (r = -0.30, P = 0.03), while in insulin-regulated diabetics, Lp(a) was also correlated with LDL-cholesterol (r = 0.20, P = 0.03). In the hypertensive patients and both diabetic groups there was no correlation of Lp(a) with coagulation or fibrinolysis parameters. These data show that Lp(a) concentrations are not related to coagulation or fibrinolysis parameters in hypertensive or diabetic patients and confirm the presence of an activated coagulation system in these patient groups.     

Reduction of serum lipoproteins in man by the oral administration of a prostaglandin analogue (enprostil)

Retrospective analysis of ulcer healing trials utilizing enprostil, a synthetic dehydroprostaglandin E2 analogue, has demonstrated a 10% or greater reduction in total serum cholesterol in 64%, 64% and 67%, respectively, of hypercholesterolemic subjects receiving the drug in doses of 70 micrograms, 35 micrograms, and 7 micrograms bid, respectively. Only 16% of subjects receiving placebo exhibited a similar reduction (P less than 0.05). The median percent changes for hypercholesterolemic patients receiving enprostil 70 micrograms, 35 micrograms, or 7 micrograms bid, and placebo were -17%, -13%, -11%, respectively, while the median percent change for those on placebo was 0% (P less than 0.05). Eight normocholesterolemic subjects participated in a double-blind crossover study comparing enprostil 70 micrograms/d with its placebo. Nine days of enprostil administration was associated with reductions in total serum cholesterol (-16%) and apolipoprotein B (-16%) and with significant reductions from baseline for LDL-cholesterol (-22%), the LDL/HDL-cholesterol ratio (-13%), and the ratio of serum apolipoprotein B to apolipoprotein A-1 (-12%). Relative to placebo, mean HDL-cholesterol, total triglycerides, and apolipoprotein A-1 concentrations remained unchanged. Daily oral administration of microgram quantities of enprostil is associated with reductions in total cholesterol, LDL-cholesterol, and apolipoprotein B suggesting therapeutic potential of this synthetic prostaglandin for the treatment of hyperlipidemia.     

Lipoprotein(a) and apolipoprotein changes after cardiac transplantation

Although lipoprotein changes after cardiac transplantation have been documented, the effects of transplantation and subsequent immunosuppressive therapy (particularly the combination of prednisone, azathioprine and cyclosporine) on apolipoprotein levels and lipoprotein(a) have not been reported. Fasting cholesterol, triglycerides, high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol, apolipoprotein A-1 and B-100 and lipoprotein(a) were evaluated in 69 consecutive patients during the waiting period before cardiac transplantation. There were 28 deaths before donor organ identification and 41 patients received a cardiac allograft. The lipoprotein levels of transplant recipients were again assayed 3 months postoperatively. Mean (+/- SEM) values increased for total plasma cholesterol (from 180 +/- 8 to 228 +/- 8 mg/dl, p less than or equal to 0.001), triglycerides (from 126 +/- 11 to 207 +/- 14 mg/dl; p less than or equal to 0.001), HDL cholesterol (from 39 +/- 2 to 49 +/- 3 mg/dl; p less than or equal to 0.002) and LDL cholesterol (from 119 +/- 7 to 138 +/- 7 mg/dl; p less than 0.02). Apolipoprotein A-1 and B-100 also increased, but lipoprotein(a) decreased from 11.7 +/- 1.7 to 6.8 +/- 1.1 mg/dl; p less than or equal to 0.0001) after transplantation. Although total cholesterol, triglycerides, LDL cholesterol, apolipoprotein A-1 and B-100 increased dramatically after cardiac transplantation, so did HDL cholesterol, thereby keeping the LDL/HDL cholesterol ratio constant. The surprising decrease in lipoprotein(a) after cardiac transplantation suggests that metabolism of lipoprotein(a) is independent of LDL cholesterol and that immunosuppressive drugs either decrease the synthesis or increase catabolism of lipoprotein(a).     

Lp(a) and lipids in adult Turner's syndrome: impact of treatment with 17beta-estradiol and norethisterone

Turner's syndrome is associated with a high incidence of cardiovascular disease and hypothyreosis; conditions which are associated with abnormal lipid metabolism. To test whether alterations of lipid metabolism is present in healthy Turner's women, we compared lipids in a group of adult women with Turner's syndrome with an age matched group of healthy women. In addition the impact of sex steroid replacement therapy was studied in the women with Turner's syndrome. Patients were studied before and during treatment with hormonal replacement therapy, consisting of either oral 17beta-estradiol or transdermal 17beta-estradiol, and oral norethisterone. Control subjects were studied once in the early follicular stage of the menstrual cycle. The study group consisted of 26 (33.2+/-7.9 years) patients with Turner's syndrome and an age matched control group of 24 (32.7+/-7.6 years) normal women. Body composition measures, apolipoprotein (apo) B and apo A-I, Lp(a), cholesterol, HDL, LDL, triglycerides, thyroxine (TT4), free thyroxine (FT4), triiodothyronine (TT3), free triiodothyronine (FT3), TSH, and leptin were determined. Apo A-I levels were higher in Turner's patients (P45 g/l) Lp(a), more women with Turner's syndrome had high levels of Lp(a) than controls (P=0.024), while all other measures of lipid metabolism were comparable to controls. The level of TSH, FT3, and FT4 were significantly higher in Turner's patients, while TT4, TT3 and adjusted 24h energy expenditure were comparable to controls. Lp(a) (P=0.005), HDL (P=0.045) and apo A-I (P=0.039) decreased significantly, while there was a tendency towards a decrease in apo B (P=0.063) during treatment with sex hormones. In conclusion more women with Turner's syndrome than controls have high levels of apolipoprotein A-I and Lp(a), but only after dichomitization, while other markers of lipid metabolism are normal. Replacement therapy with female sex hormones lowered Lp(a), HDL cholesterol and apolipoprotein A-I.     

HDL-cholesterol reductions associated with adult growth hormone replacement

OBJECTIVE: To study the effects of human growth hormone (hGH) replacement on serum lipids and lipoprotein (a) (Lp(a)) concentrations. DESIGN: A randomized double blind placebo controlled trial for 6 months followed by an open trial where all patients were treated with hGH for a further 6 months. Treatment was with recombinant hGH given in a dose of 0.125U/kg/wk increasing to 0.25U/Kg/wk. PATIENTS: Thirty two patients with growth hormone deficiency were recruited, but two withdrew because of side effects. Of the thirty patients (age 35.1 +/- 11.8 year; mean +/- SD) completing the study 13 of were assigned to the placebo group for six months and 17 to active treatment from the start. MEASUREMENTS: Fasting serum samples were analysed for total cholesterol, High density lipoprotein (HDL)-cholesterol, HDL-subfractions, triglycerides, lipoprotein (a) (Lp(a)) and IGF-1. LDL-cholesterol was calculated using the Friedewald formula. RESULTS: Compared to placebo, 6 months treatment with hGH therapy resulted in increased IGF-1 (37.6 +/- 4.1 vs. 14.0 +/- 2.2 nmol/l, P < 0.01), but there was no significant difference in any of the lipid parameters measured between placebo and active treatment groups at 6 months. hGH was associated with a decrease in HDL-cholesterol concentration from baseline to 6 months (0.97 +/- 0.08 to 0.76 +/- 0.10 mmol/l P < 0.01), especially within the HDL2 subfraction. This reduction was maintained at 12 months. There was no change in Lp(a) concentrations from 0 to 6 months (placebo -26 (-340 to 82), median and range, active -4 (-586 to 212) mg/l). There was no change in total cholesterol, LDL-cholesterol, triglycerides or proportion of HDL subfractions. CONCLUSIONS: Treatment with hGH can reduce serum HDL-cholesterol concentrations. Further investigation of this is required.     

The effect of four-year hypolipidaemic treatment on the intimal thickness of the common carotid artery in patients with familiar hyperlipidaemia.

BACKGROUND: Cholesterol lowering in patients with above-average cholesterol levels has been shown to reduce the progression of atherosclerosis. We assess the effects of lipid lowering therapy on the progression of early, preintrusive carotid arterial atherosclerosis in high risk patients with familial hyperlipidaemia free of symptomatic cardiovascular disease. METHODS: Fifty-two patients with familial hyperlipidaemia by were treated by diet and various hypolipidaemic drugs. Eighteen individuals were not taking hypolipidaemic drugs. In a prospective study by B-mode ultrasound we assessed the intima-media thickness of the distal common carotid arterial (CCA) far wall at baseline and after 4 years. RESULTS: In a subgroup of 25 patients with familial hypercholesterolaemia there was a significant decrease in total and LDL cholesterol and reduction in the intima-media thickness (IMT) of the common carotid artery from 0.78+/-0.22 mm to 0.69+/-0.17 mm (p=0.004). In a subgroup of 27 patients with familial combined hyperlipidaemia significant decreases in total and LDL cholesterol and triglycerides were associated with a decrease in the IMT of common carotid. artery from 0.72+/-0.22 mm to 0.67+/-0.15 mm (p=0.044). In 18 individuals, who were not taking hypolipidaemic drugs, there were no significant changes in the levels of cholesterol and triglycerides and in the IMT of the common carotid artery (increase from 0.58+/-0.18 mm to 0.62+/-0.13 mm, p>0.05). CONCLUSIONS: Lipid-lowering therapy in patients with familial hyperlipidaemia free of symptomatic cardiovascular disease reverses the progression of early, preintrusive atherosclerosis of the carotid artery. It is a beneficial sign indicating the possibility for atherosclerosis regression.     

The effect of atorvastatin on serum lipoproteins in acromegaly

OBJECTIVE: Acromegaly is associated with long-term adverse effects on cardiovascular mortality and morbidity. Reducing growth hormone secretion improves well-being and symptoms, but may not significantly improve the lipoprotein profile. An additional approach to cardiovascular risk reduction in acromegaly may therefore be to target lipoprotein metabolism directly. In this study we investigated the effect of statin treatment. DESIGN: Double blind, placebo-controlled, crossover study of the effects on circulating lipoproteins of atorvastatin 10 mg daily vs. placebo. Each treatment was given for 3 months in random order. SUBJECTS: Eleven patients with acromegaly. MEASUREMENTS: Lipids, lipoproteins, apolipoproteins, enzyme activity and calculated cardiovascular risk. RESULTS: Atorvastatin treatment compared to placebo resulted in a significant decrease in serum cholesterol (5.85 +/- 1.04 mmol/l vs. 4.22 +/- 0.69 mmol/l; mean +/- SD; P < 0.001), low-density lipoprotein (LDL) cholesterol (2.95 +/- 1.07 mmol/l vs. 1.82 +/- 0.92 mmol/l; P < 0.001), very low-density lipoprotein (VLDL) cholesterol (0.31 (0.21-0.47) mmol vs. 0.23 (0.13-0.30) mmol/l median (interquartile range); P < 0.05), apolipoprotein B (111 +/- 28 mg/dl vs. 80 +/- 18 mg/dl; P < 0.001), and calculated coronary heart disease risk (6.8 (3.3-17.9) vs. 2.8 (1.5-5.7)% over next 10 years; P < 0.01). Serum triglyceride was 1.34 (1.06-1.71) mmol/l on placebo and 1.14 (0.88-1.48) mmol/l on atorvastatin (ns). HDL cholesterol, apolipoprotein A1 and Lp(a) concentrations and cholesteryl ester transfer protein and lecithin: cholesterol acyl transferase activities were also not significantly altered. CONCLUSION: Atorvastatin treatment was safe, well tolerated and effective in improving the atherogenic lipoprotein profile in acromegaly.