Biomedical subjects

D O'Neal

Publications and source records attributed to D O'Neal.

13 recordsLinked to original sources

PubMed2000

Treating elevated lipids. Does it make a difference?

BACKGROUND: There is now abundant evidence from clinical trials that treatment with lipid modifying therapy will decrease the risk of coronary heart disease (CHD). The decision to treat a patient, whether with advice on lifestyle modification or with drug therapy, needs to be based on consideration of costs versus benefits. OBJECTIVE: To assess the evidence from primary and secondary prevention studies for cardiovascular benefit of cholesterol lowering medication. DISCUSSION: Treating hypercholesterolaemia reduces the relative risk of major CHD events by about 30%. The greatest benefit of lipid lowering treatment is in the high risk group. This group shows the greatest reduction in absolute risk and therefore a 'smaller number to treat' to prevent one major CHD event. In the moderate risk group three times as many individuals require treatment to prevent one major CHD event. However, this corresponds to the benefit in primary prevention of stroke by treating mild-moderate hypertension in middle aged men.

Coronary Disease↗

PubMed1998

Growth hormone deficiency and cardiovascular risk.

It is now recognized that growth hormone (GH) deficiency in adults represents a distinct clinical syndrome that encompasses reduced psychological well-being as well as specific metabolic abnormalities. The latter features, which include hypertension, central obesity, insulin resistance, dyslipidaemia and coagulopathy, closely resemble those of metabolic insulin resistance syndrome. The increased cardiovascular morbidity and mortality demonstrated in these GH-deficient (GHD) adults reinforce the close association between the two syndromes. Replacement of GH in GHD adults has resulted in a marked reduction of central obesity and significant reduction in total cholesterol but little change in other risk factors, in particular insulin resistance and dyslipidaemia. The persistent insulin resistance and dyslipidaemia, together with the elevation of plasma insulin levels and lipoprotein (a) with GH replacement in these subjects are of concern. Long-term follow-up data are required to assess the impact of GH replacement on the cardiovascular morbidity and mortality of GHD adults. Further exploration of the appropriateness of the GH dosage regimens currently being employed is also indicated.

Adult↗

PubMed1998

A comparison of LDL size determination using gradient gel electrophoresis and light-scattering methods.

This study compared gradient gel electrophoresis (GGE) and light-scattering (LS) methods of determining low density lipoprotein (LDL) particle size. LDL was isolated from 27 fasting subjects. Peak particle size was determined by GGE on 3-13% gradient gels (Gradipore, Sydney, Australia) and by LS using a Zetasizer 3000 (Malvern Instruments, Malvern, UK). Repeated measurements on a single specimen indicated a coefficient of variation (CV) of 0.3%. A correlation was noted (P < 0.0001; r = 0.78) when comparing LDL particle size determined by LS methodology and GGE. Particle diameter results obtained by LS were smaller than those obtained by GGE (23.1 +/- 0.1 vs. 26.1 +/- 0.1 nm; P < 0.0001). LDL particle size determined by LS methodology correlated inversely with the log of triglyceride level (P < 0.0001; r = -0.77) and positively with high density lipoprotein (HDL) cholesterol level (P < 0.002; r = 0.57).

Cholesterol, HDL↗

PubMed1997

The role of abdominal adiposity and insulin resistance in dyslipidemia of chronic renal failure.

The atherogenic profile of high triglyceride, reduced high-density lipoprotein (HDL) cholesterol, and small low-density lipoprotein particle size found in patients on chronic hemodialysis is known to be associated with insulin resistance and abdominal obesity in the general population. To assess the influence of insulin resistance and abdominal adiposity on the lipid profile in subjects on hemodialysis, intravenous glucose tolerance test and dual-energy x-ray absorptiometry were performed in 26 nondiabetic subjects on hemodialysis and compared with 22 nondiabetic control subjects matched for age, sex, and body mass index. Subjects on hemodialysis were found to have higher triglyceride (133 mg/dL [95% confidence interval, 115 to 159 mg/dL] v 97 mg/dL [95% confidence interval, 80 to 124 mg/dL]; P < 0.05), lower HDL cholesterol (36 +/- 3 mg/dL v 51 +/- 4 mg/dL [mean +/- SEM]; P < 0.01), enhanced insulin response to glucose (2.72 +/- 0.28 mUL(-1) min per mg dL(-1) v 1.67 +/- 0.22 mUL(-1) min per mg dL(-1); P < 0.01), and reduced sensitivity to the action of insulin (2.24 min(-1) per mUL(-1) min [95% confidence interval, 1.86 to 2.75 min(-1) per mUL(-1) min] v 4.17 min(-1) mUL(-1) min [95% confidence interval, 2.95 to 5.9 min(-1) per mUL(-1) min]; P < 0.01) than the control subjects. Abdominal adiposity measured by dual-energy x-ray absorptiometry (2,004 +/- 210 g v 2,163 +/- 198 g [mean +/- SEM]; P = NS) and percentage of body fat distributed to the abdomen (10.5% +/- 0.3% v 9.7% +/- 0.5% [mean +/- SEM]; P = NS) did not differ between the two groups. Subjects on hemodialysis were insulin resistant, but unlike control subjects, their lipid profile was not predicted by their insulin sensitivity. Abdominal adiposity was associated with a deteriorating lipid profile and insulin resistance in subjects on hemodialysis, as it was in control subjects. The presence of renal failure resulted in additional insulin resistance and a higher triglyceride level in the leaner subjects on hemodialysis compared with control subjects with similar levels of abdominal fat. In the more obese subjects, insulin sensitivity and triglyceride level did not differ between the two groups of subjects, although HDL cholesterol level remained low in subjects on hemodialysis. In conclusion, insulin resistance in subjects on hemodialysis did not directly account for their abnormal lipid profile. The negative impact of abdominal adiposity on the metabolic profile was preserved in subjects on hemodialysis, but the presence of renal failure itself resulted in insulin resistance in the leaner subjects and dyslipidemia in all subjects on hemodialysis compared with control subjects of comparable abdominal adiposity.

Abdomen↗

PubMed1997

High density lipoprotein (HDL) particle composition in patients with end stage renal failure (ESRF) on chronic dialysis.

BACKGROUND: Hypertriglyceridaemia, low high density lipoprotein (HDL) cholesterol level and reduced LDL particle size are the major features of uraemic dyslipidaemia. They are also found in the Insulin Resistance Syndrome. AIM: To examine alterations in HDL composition in patients on chronic dialysis and their relationship with insulin resistance. METHODS: HDL particle size was determined in 33 patients on chronic haemodialysis (HD), 27 on chronic ambulatory peritoneal dialysis (CAPD) and 32 control non-diabetic subjects (C) without renal disease by non-denaturing 3-30% polyacrylamide gradient gel electrophoresis. A weighted HDL particle size score was calculated taking into account both HDL particle size and percentage total HDL protein concentration of each HDL band of the individual. Lipid and apolipoliprotein concentrations were determined in HDL2 and HDL3 particles obtained by sequential ultracentrifugation. In a subset of 24 control subjects and 22 subjects on HD, insulin sensitivity was also determined by an intravenous glucose tolerance test (IVGTT). RESULTS: HDL particles were found to be more triglyceride enriched and apoAI depleted in subjects on HD even though plasma triglyceride level was highest in patients on CAPD. Five subpopulations of HDL particles were identified by gradient gel electrophoresis in all subjects combined. In the subgroup of subjects who underwent IVGTT, the weighted HDL particle size score correlated positively with HDL cholesterol level (r = 0.6, p < 0.0005), LDL particle size (r = 0.47, p < 0.001), and insulin sensitivity (r = 0.48, p < 0.001), and negatively with plasma triglyceride level (r = 0.37, p < 0.01). CONCLUSIONS: We conclude that even though HDL cholesterol is reduced to a similar level in subjects on both forms of dialysis for end stage renal failure, abnormalities of HDL composition are more marked in subjects on HD. Reduction in HDL particle size is linked with insulin resistance and accompanies reduction in LDL particle size and hypertriglyceridaemia.

Cholesterol, HDL↗

PubMed1996

Low-density lipoprotein particle size distribution in end-stage renal disease treated with hemodialysis or peritoneal dialysis.

Dyslipidemia accompanies end-stage renal disease (ESRD) and contributes to the high incidence of cardiovascular disease in patients on chronic dialysis treatment. The lipid abnormalities of elevated triglyceride level and reduced high-density lipoprotein cholesterol level that occur in ESRD are associated in the normal population with an altered distribution of low-density lipoprotein (LDL) particle size, a pattern associated with increased risk of coronary heart disease. To assess the effect of ESRD on LDL particle size distribution, we examined plasma lipid levels and LDL particle size in 43 subjects on chronic hemodialysis, 23 subjects on continuous ambulatory peritoneal dialysis, and 30 control subjects with normal renal function. Of subjects on continuous ambulatory peritoneal dialysis, 48% had small LDL particle size compared with 23% of subjects on hemodialysis and 7% of control subjects. Subjects on both forms of dialysis also had higher triglyceride levels and lower high-density lipoprotein cholesterol levels that correlated with LDL particle size. We conclude that altered LDL particle size forms an important component of the metabolic abnormalities that contribute to the increased cardiovascular risk found in ESRD.

Case-Control Studies↗

PubMed1996

Low density lipoprotein particle size in hypopituitary adults receiving conventional hormone replacement therapy.

Adults receiving conventional replacement therapy for hypopituitarism are known to have increased cardiovascular mortality. The aim of this study was to assess the lipid profiles of 30 hypopituitary adults compared with 2 case control groups, 1 matched for age, sex, and body mass index (BMI) and the second matched for age and sex only with a BMI representative of the general population. Fasting lipids, lipoproteins, and apoproteins (Apo) were determined by routine methods. Low density lipoprotein (LDL) particle size was determined by nondenaturing gradient gel electrophoresis. LDL size was significantly smaller in the hypopituitary group (25.9 +/- 0.1 nm) than in the BMI-matched (26.2 +/- 0.1 nm; P < 0.05) and standard control (26.3 +/- 0.1 nm; P < 0.01) groups. High density lipoprotein cholesterol levels in the hypopituitary group were significantly lower than those in the BMI-matched control group (1.13 +/- 0.06 vs. 1.34 +/- 0.06 mmol/L; P < 0.05) and the standard control group (1.38 +/- 0.06 mmol/L; P < 0.005). Apo A1 levels were also lower compared with those in the BMI-matched (122 +/- 6 vs. 137 +/- 4 mg/dL; P < 0.05) and the standard (143 +/- 4 mg/dL; P < 0.005) control groups. There was a trend toward higher triglyceride levels when the hypopituitary subjects were compared with the standard control group [1.4 (95% CI, 1.3-2.2) vs. 1.0 (95% CI, 0.9-1.4) mmol/L; P = 0.06]. These differences were more marked in the female subjects studied. No significant differences were noted in total cholesterol, LDL cholesterol, or Apo B levels. We conclude that hypopituitary patients receiving conventional replacement therapy have an atherogenic lipid profile characterized by small dense LDL, decreased high density lipoprotein cholesterol, and increased triglyceride levels, which may contribute to the excess cardiovascular mortality in this group.

Adult↗

PubMed1996

Factors influencing Lp[a]- particle size as determined by gradient gel electrophoresis.

This study examined factors influencing the particle diameter of Lp[a]-, the low density lipoprotein (LDL)-like moiety of Lp[a], in 26 subjects chosen to provide a range of Lp[a] and triglyceride levels. Lp[a] and LDL fractions were isolated by vertical density ultracentrifugation. Lp[a] was further purified using a lysine-Sepharose affinity column and Lp[a]- obtained by incubating Lp[a] with dithiothreitol. Lp[a], LDL, and Lp[a]- fractions were run on 3-13% gradient gels to determine particle diameter. Lp[a] size correlated positively with LDL size (r = 0.62; P < 0.001), but the association between Lp[a]- size and LDL size was stronger (r = 0.82; P < 0.0001). Log triglyceride level correlated inversely with Lp[a]- size (r = -0.72; P < 0.0001) and LDL size (r = 0.69; P < 0.0001). HDL cholesterol level correlated positively with Lp[a]- size (r = 0.67; P < 0.0005) and LDL size (r = 0.64; P < 0.0005). The strong correlation between LDL size and Lp[a]- size may be due to extracellular utilization of circulating LDL in the production of Lp[a] or may reflect the same metabolic processes influencing both these particles once Lp[a] has been formed.

Apolipoproteins A↗

PubMed1992