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Biomedical subjects

P N Durrington

Publications and source records attributed to P N Durrington.

At least 109 records · Page 6Linked to original sources
PubMed1994

Effects of a new fish oil concentrate on plasma lipids and lipoproteins in patients with hypertriglyceridaemia.

OBJECTIVES: The effect of a fish oil preparation, K-85, in which the omega-3 fatty acid content was concentrated to 92% of total fat, on serum lipid and lipoprotein concentrations was investigated in patients with primary hypertriglyceridaemia. DESIGN: The study was a randomized, double-blind, placebo-controlled study. SETTING: Seven centres participated in the study, five secondary referral centres and two general practices. SUBJECTS: Men and women aged 18-70 years with fasting serum triglyceride concentrations between 2 and 10 mmol/l and fasting serum cholesterol concentrations > 5.2 mmol/l were studied. Patients with diabetes mellitus, hypothyroidism, serious illness in the previous 3 months or severe concurrent illness were excluded from the study, as were drug or alcohol abusers and pregnant and lactating women. Ninety-five subjects entered the study, 79 completed the study. INTERVENTIONS: Patients were randomized to receive K-85 2 g twice daily or corn oil 2 g twice daily for 14 weeks. MAIN OUTCOME MEASUREMENTS: The serum concentrations of triglycerides and cholesterol, very low-density lipoprotein (VLDL), low-density lipoprotein (LDL), high-density lipoprotein (HDL) and lipoprotein (a). Fasting blood glucose and blood pressure. RESULTS: Serum triglycerides and VLDL-cholesterol were significantly lower in the group treated with K-85 than in the placebo group after 6, 10 and 14 weeks (all P < 0.01) and there was a decrease in the serum triglyceride concentration from 3.99 (2.94-9.47) to 2.87 (1.2-9.93) mmol/l (P < 0.001) and in VLDL-cholesterol from 1.47 (0.77-3.63) to 1.12 (0.21-3.67) mmol/l (P < 0.01) in patients receiving K-85. Serum HDL-cholesterol increased from 0.98 (0.95-1.01) to 1.11 (1.07-1.15) mmol/l (P < 0.01) in the patients with type IV hyperlipoproteinaemia but did not change in those with type IIb. Serum LDL-cholesterol, lipoprotein (a) and fasting blood glucose were unaffected by K-85. Diastolic blood pressure decreased from 86 +/- 11 to 80 +/- 12 mmHg (P < 0.02) and was also lower than in the placebo group (P < 0.05). The corn oil placebo did not affect any of the parameters. CONCLUSION: K-85 is effective in lowering serum triglycerides and VLDL in patients with primary hypertriglyceridaemia and may have utility as a triglyceride-lowering agent.

Adult↗
PubMed1994

A prospective study of serum lipoproteins after coronary artery bypass surgery.

We examined the acute and long-term effects of coronary artery bypass (CABG) surgery on serum lipid, lipoprotein and apolipoprotein levels. One series of 34 patients having CABG surgery was studied pre-operatively and for six weeks afterwards, and another 22 patients were investigated before and two years after CABG surgery. None of the patients studied received any lipid-lowering drug therapy or specific dietary advice. In both groups, pre-operative serum lipoprotein (a) (Lp(a)) and serum triglyceride concentrations were raised and serum high-density lipoprotein (HDL) cholesterol and apolipoprotein AI (apo AI) were low compared to healthy people. Acutely, there were profound decreases of 40-60% in the serum levels of cholesterol (p < 0.001), low-density lipoprotein cholesterol (p < 0.05), triglycerides (p < 0.01), Lp(a) (p < 0.05) and apolipoprotein B (apo B) (p < 0.05). There was a small decrease in serum apo A1 (p < 0.05), and serum HDL cholesterol showed no change. All these variables regained their pre-operative values within six weeks. Two years postoperatively, serum Lpa was 40% less than its pre-operative concentration (p < 0.001) and HDL cholesterol had increased (p < 0.001). Triglyceride levels decreased (p < 0.02) when beta-blockade was withdrawn. The long-term decrease in Lp(a) following surgery is unlikely to be due either to stopping beta-blockers or to life-style changes. Myocardial ischaemia relieved by the operation may have been partially responsible for its previously raised concentration.

Adult↗
PubMed1993

The role of high-density lipoprotein and lipid-soluble antioxidant vitamins in inhibiting low-density lipoprotein oxidation.

1. The oxidation of low-density lipoprotein (LDL) is believed to play a central role in atherogenesis. We have compared the effect of antioxidant vitamins and high-density lipoprotein (HDL) on the Cu(2+)-catalysed oxidation of LDL. 2. Antioxidant vitamin supplementation significantly reduced conjugated diene formation but did not affect the formation of lipid peroxides. 3. Conversely, HDL did not affect conjugated diene formation but inhibited the formation of lipid peroxides by up to 90%. 4. The inhibition by HDL of lipid peroxide formation in oxidized LDL was dependent on the concentration of HDL and was not due to HDL chelating Cu2+. 5. Large interindividual variations in the inhibition of lipid peroxide formation by autologous HDL were evident, which were related to the rate of lipid peroxide generation in the LDL. 6. We conclude that HDL is a powerful antioxidant or more probably inhibitor of LDL oxidation in vitro and may play an important role in vivo in preventing atherosclerosis by inhibiting LDL oxidation in the artery wall.

Adult↗
PubMed1993

Increased transfer of cholesteryl esters from high density lipoproteins to low density and very low density lipoproteins in patients with angiographic evidence of coronary artery disease.

Cholesterol esterification, transfer of cholesteryl esters from high density lipoproteins to very low density and low density lipoproteins (VLDL/LDL) and the composition of lipoproteins isolated by density gradient ultracentrifugation have been investigated in 18 men with angiographic evidence of severe coronary artery disease and in 27 healthy men without coronary artery disease. Patients had significantly higher serum cholesterol (P < 0.001), serum triglycerides (P < 0.02) and lower high density lipoprotein cholesterol (HDL) (P < 0.04) compared with healthy men. The transfer of cholesteryl ester from HDL to VLDL and LDL was 27.8 +/- 12.2 nmol/ml per h (mean +/- S.D.) in patients and was significantly higher than the value of 17.8 +/- 6.5 nmol/ml per h obtained in healthy men (P < 0.003) or 17.1 +/- 7.6 nmol/ml per h) in 16 controls (P < 0.03) with similar serum cholesterol and triglyceride concentrations. Lipoprotein protein concentrations were significantly higher in LDL (P < 0.05) and small VLDL (P < 0.01) in patients. In addition, patient LDL and large VLDL contained more free cholesterol than matched controls (P < 0.01, P < 0.05, respectively). This was reflected in the increased free cholesterol/phospholipid ratio (a measure of lipoprotein surface composition) in LDL (P < 0.002). These findings indicate that patients with established coronary artery disease have increased transfer of cholesteryl ester from HDL to VLDL and LDL, which is independent of serum triglyceride concentrations. This increased transfer of cholesteryl ester may be a result of the increased free cholesterol content of very low density lipoproteins.

Adult↗
PubMed1993

Is paraoxonase related to atherosclerosis.

Human serum paraoxonase is responsible for the hydrolysis of organophosphate anticholinesterases, however, whether the enzyme has a physiological role other than the detoxication of insecticides and nerve gases has remained uncertain. Recently, evidence has begun to accumulate of a relationship between the serum activity of paraoxonase and atherosclerosis. Paraoxonase may a fundamental role in lipoprotein metabolism, preventing oxidative changes to low-density lipoprotein which render the particle atherogenic.

Arteriosclerosis↗
PubMed1993

The immediate effect of streptokinase on serum lipoprotein(a) concentration and the effect of myocardial infarction on serum lipoprotein(a), apolipoproteins A1 and B, lipids and C-reactive protein.

Lipoprotein(a) (Lp(a)) has close structural homology with plasminogen and, at least in vitro, may interfere with fibrinolysis. Any changes in the serum Lp(a) concentration during and following myocardial infarction (MI) and whether the serum Lp(a) level is affected by streptokinase (SK) are therefore of interest. Serum Lp(a) levels immediately before and 3 h after completion of an intravenous infusion of SK in 39 patients with acute MI were not significantly different (median 31.3 mg/dl before and 35.9 mg/dl after). Furthermore, SK added during the serum Lp(a) assay did not affect the result, except at very high concentrations of SK (1000 units/ml). Serum Lp(a) and fasting lipids were measured daily for 3 days following definite MI in 13 patients and then after 14 and 42 days. There was no significant change in serum Lp(a) following MI. In marked contrast, C-reactive protein levels in these patients increased steeply immediately following MI. Thus, there was no early 'acute-phase response' in serum Lp(a) levels after MI. However, greater variation in its concentration was observed at day 14 than at other times. Serum cholesterol, apolipoprotein B and apolipoprotein A1 concentrations decreased significantly following MI, whereas a significant transient increase in serum triglycerides occurred. Forty-two days after MI all lipid and lipoprotein values had regained their day 1 levels, except for apo A1, which remained depressed.

Aged↗
PubMed1993

Protection of low-density lipoprotein against oxidative modification by high-density lipoprotein associated paraoxonase.

We have investigated the Cu2+ induced generation of lipid peroxides in low density lipoprotein (LDL) incubated with high density lipoprotein (HDL) and with purified paraoxonase, an enzyme normally resident on HDL. HDL (1.5 mg) and paraoxonase (20 micrograms) inhibited lipid peroxide generation in LDL by 32% and 25%, respectively after 24 h of incubation (both P < 0.01). The decrease in LDL lipid peroxides both with HDL and with paraoxonase were concentration dependent. The degree of protection offered by HDL tended to relate to its paraoxonase activity (R = 0.47; P < 0.06). Neither purified paraoxonase nor HDL chelated Cu2+ sufficiently to account for the decrease in LDL oxidation. Purified paraoxonase did not affect LDL oxidation when it had been heat inactivated. Mass transfer of lipid peroxides from LDL to HDL did not explain the protection of LDL against oxidation: the total lipid peroxides accumulating during incubation was decreased both by HDL and by paraoxonase. These results suggest a direct role for HDL in preventing atherosclerosis probably by an enzymic process which prevents the accumulation of lipid peroxides on LDL. Paraoxonase is an example of an enzyme which might possibly be involved.

Aryldialkylphosphatase↗
PubMed1993

Relationship between serum butyrylcholinesterase activity, hypertriglyceridaemia and insulin sensitivity in diabetes mellitus.

1. The activity of serum butyrylcholinesterase ('pseudocholinesterase', EC3.1.1.8) was investigated in 56 patients with type 1 diabetes mellitus, 51 patients with type 2 diabetes mellitus and 101 healthy control subjects. 2. Butyrylcholinesterase activity was significantly elevated in both type 1 (8.10 +/- 3.35 units/ml) and type 2 (7.22 +/- 1.95 units/ml) diabetes compared with the control subjects (4.23 +/- 1.89 units/ml) (P < 0.001). 3. In the patients with type 1 and type 2 diabetes, serum butyrylcholinesterase activity was correlated with log serum fasting triacylglycerol concentration (r = 0.41 and r = 0.43, respectively, P < 0.001). In the type 2 population serum butyrylcholinesterase activity was also correlated with insulin sensitivity (r = -0.51, P < 0.001). 4. Serum butyrylcholinesterase activity was unrelated to age, gender, serum gamma-glutamyltranspeptidase activity, body mass index, or treatment for diabetes in both the diabetic populations. 5. In 37 non-diabetic patients with butyrylcholinesterase deficiency serum triacylglycerol levels were in the normal range. 6. These results are consistent with the view that butyrylcholinesterase may have a role in the altered lipoprotein metabolism in hypertriglyceridaemia associated with insulin insensitivity or insulin deficiency in diabetes mellitus.

Butyrylcholinesterase↗
PubMed1993

An evaluation of the Reflotron for the determination of plasma cholesterol in capillary blood. Effect of operator variability.

The availability of portable analysers potentially puts the detection of individuals with high serum cholesterol levels on a similar footing to that of high blood pressure. The Reflotron, which can make cholesterol measurements on capillary blood samples without the need for centrifugation, has been evaluated in clinical practice. In 94 consecutive patients capillary blood was used for the determination of serum cholesterol by the Reflotron, by a laboratory technician (n = 37) and by a nursing sister (n = 57). Venous blood was also taken from the same patients within a few minutes of the capillary sample for enzymic determination of serum cholesterol at the hospital laboratory. Overall, the Reflotron values were about 0.6 mmol/l lower than those obtained at the hospital laboratory. The accuracy and precision of the results obtained by the nurse were poorer than those obtained by the technician, even though the nurse had attended a three day training course. Our results indicate that the Reflotron is a suitable instrument for use in screening for serum cholesterol, provided personnel operating the machine have adequate training and experience, and provided it is borne in mind that the results obtained may be slightly lower than standard laboratory methods.

Capillaries↗
PubMed1993

Serum lipoprotein (a) concentrations in patients undergoing continuous ambulatory peritoneal dialysis.

Lipoprotein (a) is a subspecies of low-density lipoprotein which possesses as part of its protein moiety a mutant form of plasminogen termed apolipoprotein (a), and which may be closely related to the risk of ischaemic heart disease and cerebral infarction. We have investigated the serum concentrations of lipoprotein (a) and other lipoproteins in 24 male patients on CAPD and compared them to healthy men (n = 100) and to age-matched healthy controls (n = 38). The most striking finding was a substantial elevation of serum lipoprotein (a) in CAPD patients in whom it was 46.9 (2.2-168) mg/dl (median and range) compared to 9.0 (< 0.6-87.4) mg/dl in healthy control group and 6.7 (< 0.6-84.2) mg/dl in age-matched controls (both P < 0.001). Patients, when compared to healthy men, also had significantly increased serum triglycerides (median and range, 1.94 (0.55-8.00) versus 1.24 (0.36-4.40) mmol/l; P < 0.001), very-low-density lipoprotein cholesterol (median and range, 0.98 (0.10-3.71) versus 0.46 (0.10-1.17) mmol/l; P < 0.001), and lower-high-density lipoprotein cholesterol (mean +/- 1 SD, 1.26 +/- 0.29 versus 1.35 +/- 0.31 mmol/l). Of these, however, only the difference in very-low-density lipoprotein cholesterol remained statistically significant (P < 0.001) in comparison to age-matched controls. The marked elevation of serum lipoprotein (a) in patients on CAPD may be due to increased hepatic synthesis as a consequence of the substantial amounts of plasma proteins lost in the dialysate. Elevated serum lipoprotein (a) concentrations in CAPD patients may contribute to their risk of coronary artery disease.

Adult↗
PubMed1993

Management of hyperlipidaemia: guidelines of the British Hyperlipidaemia Association.

There is considerable evidence to suggest that the identification and treatment of dyslipidaemia will reduce the risk of premature CHD, i.e. before the age of 65. Diagnosis of the cause of raised plasma lipid levels will enable appropriate decisions to be taken with regard to management. The cornerstone of treatment is nutritional counselling and attention to other major risk factors for CHD, particularly smoking and hypertension. For a small percentage of patients with severe hyperlipidaemia drug therapy is indicated. Appropriate drug choices need to be made based on the particular lipid abnormality to be treated. In general those patients with clinical vascular disease are treated more aggressively than those where the aim is primary prevention. More research is needed to determine individual risk more precisely and to allow proper targeting of therapy. Genetic factors, qualitative changes in lipoproteins, lipoprotein (a), fibrinogen, and other coagulation and thrombotic factors are likely to be important in individual risk assessment. There is no doubt that more information is needed from prospective studies of lipid-lowering therapy in terms of risk benefit for affected individuals. Hopefully the major studies currently underway will fill some of the gaps in our knowledge. Until then aggressive therapy with drugs should be reserved for those at highest risk where the benefit is likely to be greatest.

Cholesterol, Dietary↗
PubMed1993

Serum lipoprotein (a) in renal transplant recipients receiving cyclosporin monotherapy.

Coronary heart disease is more common in patients with chronic renal failure and is a major cause of death after renal transplantation. Elevated serum lipoprotein (a) (Lp(a)) is a known risk factor for coronary heart disease in the general population. We measured the serum concentration of Lp(a) in 58 renal transplant recipients (40 male, 18 female) on cyclosporin monotherapy, and in 58 age- and sex-matched controls. Serum Lp(a) was significantly elevated in the transplant patients with a median of 27.5 (range < 0.8-140.3) mg/dl compared to 7.6 (range < 0.8-87.4) mg/dl in controls (P < 0.001). Total serum cholesterol, low-density lipoprotein cholesterol, and total triglyceride concentrations were also significantly raised (P < 0.001) in the transplant recipients. The increased serum Lp(a) may contribute to the increased cardiovascular morbidity associated with renal transplantation.

Adult↗
PubMed1993

Diabetes, hypertension and hyperlipidaemia.

The predominant cause of death among diabetic patients in populations with high cholesterol levels is coronary heart disease. This effect is related to diet and both insulin dependent and non-dependent diabetes are characterized by an increase in circulating very low density lipoprotein (VLDL). Insulin deficiency or resistance accelerates the release of VLDL from the liver. However, the susceptibility to vascular disease seen among diabetics may be a particular function of their raised levels of intermediate density lipoproteins (IDL) produced when VLDL is metabolised to low density lipoprotein. The concept of hyperinsulinaemia is not helpful in explaining the diabetic patient's disturbed metabolism and is a source of confusion. The major therapeutic task in non-insulin-dependent diabetes is often to reduce the patient's weight and thus to reduce insulin resistance. In patients with coronary heart disease, this should be fully investigated at least as promptly as in non-diabetic people. Lipid lowering drugs, and particularly the fibrates, are suitable for treating diabetic patients since they lower both cholesterol and triglycerides and raise HDL. There is much more controversy about the ideal choice of antihypertensive agents, particularly for patients with only moderate increases in blood pressure. Both thiazides and beta-blockers disturb the lipid profile most markedly in many patients with diabetes or primary hyperlipidaemia. Current evidence suggests that many patients with hypertension, but no other cardiovascular risk factors, derive no benefit from receiving antihypertensive therapy. As in the management of hypercholesterolaemia, the decision to introduce drug therapy should not be determined by the blood pressure reading alone, but should take account of the whole patient risk. The combination of even "mild" hypertension with diabetes or hyperlipidaemia demands greater therapeutic activity and then there is a case for the use of antihypertensive agents which do not adversely influence the lipid profile.

Antihypertensive Agents↗
PubMed1992

Treatment of familial hypercholesterolaemia. United Kingdom lipid clinics study of pravastatin and cholestyramine.

OBJECTIVE: To compare the efficacy and safety of cholestyramine, an anion exchange resin, and pravastatin, a new hydrophilic specific inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, in the treatment of heterozygous familial hypercholesterolaemia. DESIGN: Double blind, double dummy, placebo controlled study with three parallel groups. SETTING: Six specialist lipid clinics in the United Kingdom. PATIENTS: 128 patients aged 18-70 with heterozygous familial hypercholesterolaemia diagnosed on strict biochemical and clinical findings. MAIN OUTCOME MEASURES: Total plasma cholesterol, triglyceride, and lipoprotein subfractions and biochemical and haematological safety parameters. RESULTS: Pravastatin (40 mg/day) led to a 25% reduction in total plasma cholesterol concentration and a reduction in low density lipoprotein cholesterol concentration of 30%. Cholestyramine (24 g/day) led to similar reductions in concentrations of total cholesterol (23%) and low density lipoprotein cholesterol (31%). No consistent changes occurred in high density lipoprotein cholesterol values with either compound. Plasma triglyceride concentrations showed a small rise (18%) on resin therapy. No serious adverse drug reactions occurred during the study. CONCLUSIONS: Pravastatin seems to be a highly effective, well tolerated drug for severe hypercholesterolaemia. Patients chosen for this study were recruited on the basis that they could tolerate a full dose of cholestyramine, and in this situation cholestyramine was also highly effective in lowering plasma low density lipoprotein cholesterol concentrations.

Adolescent↗