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Biomedical subjects

L A Simons

Publications and source records attributed to L A Simons.

At least 19 recordsLinked to original sources
PubMed1992

Triglyceride levels and the risk of coronary artery disease: a view from Australia.

A prospective study of cardiovascular disease in elderly Australians commenced in 1988 in Dubbo, New South Wales. The study population comprised 1,237 men and 1,568 women aged > or = 60 years. The prevalence rates of coronary artery disease (CAD) and putative risk factors were examined cross-sectionally in the baseline data. The age-standardized rate of CAD was 23.8/100 men and 18.1/100 women. In a univariate analysis, the major risk factors for CAD were hypertension, diabetes, family history, reduced high-density lipoprotein (HDL) cholesterol levels, and increased triglyceride levels. The prevalence rate of CAD was examined in those with low-density lipoprotein (LDL):HDL ratios < 5.0 or > 5.0. Most notably in women, the CAD rate was 16/100 with an LDL.HDL ratio < or = 5.0 and 28/100 with an LDL.HDL ratio > 5.0. In the latter group, the rate was 21/100 in those with triglycerides < or = 2.3 mmol/liter and 36/100 in those with triglycerides > 2.3 mmol/liter. In a multiple logistic model that controlled for many potential risk factors or confounding variables, CAD in men was significantly predicted by age, hypertension (odds ratio = 1.40), family history (odds ratio = 2.05), and low HDL cholesterol (odds ratio = 0.78). Significant predictors in women were age, years of education (odds ratio = 0.82), hypertension (odds ratio = 1.45), family history (odds ratio = 1.77), serum triglycerides (odds ratio = 1.30), and low HDL cholesterol (odds ratio = 0.73). An independent gradient of CAD risk with increasing triglyceride levels and a similar gradient with decreasing HDL cholesterol levels were found in women.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1992

Treatment of primary hypercholesterolaemia with pravastatin: efficacy and safety over three years.

OBJECTIVE: To assess the efficacy, safety and tolerability of pravastatin over three years of treatment. DESIGN: An open, multicentre randomised study. SETTING: Subjects receiving tertiary care at three hospital lipid clinics. PATIENTS: Subjects with primary hypercholesterolaemia (type IIa) or combined hyperlipidaemia (type IIb), already stabilised on a cholesterol-lowering diet, with low density lipoprotein (LDL) cholesterol levels of greater than 4.7 mmol/L and triglyceride levels of less than 4.5 mmol/L. Sixty-one subjects were randomly assigned to the treatment groups: 60 completed 12 weeks and 46 completed 30-36 months of treatment. INTERVENTIONS: Subjects were randomly assigned to receive either pravastatin 20 mg/day, pravastatin 40 mg/day or cholestyramine 16 g/day for a period of 12 weeks. Subsequently, dose titration of pravastatin up to 40 mg/day was permitted, if required, and all groups received supplementary therapy with other lipid-lowering drugs. MAIN OUTCOME MEASURES: Lipids, lipoproteins, haematological and biochemical safety parameters were measured at regular intervals. Adverse events were monitored. RESULTS: There were significant reductions in total and LDL cholesterol levels with all treatments over 12 weeks (P < 0.001). The mean reductions (+/- SD) in LDL cholesterol were 26% +/- 14% in the group taking pravastatin 20 mg/day (n = 21), 30% +/- 8% in the group taking pravastatin 40 mg/day (n = 21) and 34% +/- 13% in the group taking resin (n = 18). The percentage changes in LDL cholesterol were independent of age, baseline cholesterol level or lipid phenotype. High density lipoprotein (HDL) cholesterol levels were significantly increased, by 8%-18% with all treatments (P < 0.001). Triglyceride levels were reduced by high-dose pravastatin only (7% +/- 29%), but were found to increase with resin (45% +/- 63%). During long-term treatment over 36 months, still greater reductions in total and LDL cholesterol were found in patients taking pravastatin (n = 35), but not in those taking resin (n = 11). There was an apparent decrease in effect beyond 18 months in both groups, possibly related to reduced compliance with diet or cholestyramine intake. Eight subjects allocated to pravastatin and seven allocated to resin withdrew (one and two subjects respectively because of drug-induced adverse events). Adverse events during 12 weeks' monotherapy with pravastatin included central nervous system (CNS) symptoms (12%), gastrointestinal (GIT) symptoms (7%) and an acute hepatitic reaction (one subject). Of those in the resin therapy group, 22% developed GIT symptoms. Myalgia occurred in three subjects using a combination of pravastatin and clofibrate, but this resolved fully upon clofibrate withdrawal. CONCLUSIONS: Pravastatin was found to be a relatively effective, safe and well tolerated lipid-lowering drug. Still greater LDL reduction was achieved with pravastatin combination therapy and this was essentially maintained over three years.

Adult↗
PubMed1992

Successful management of primary hypercholesterolaemia with simvastatin and low-dose colestipol.

OBJECTIVE: To examine whether a small dose of bile acid sequestrant used in combination with a hydroxymethylglutaryl coenzyme A reductase inhibitor is more effective in reducing serum and low-density lipoprotein (LDL) cholesterol levels than inhibitor used alone. DESIGN: A randomised, double-blind study. SETTING: Subjects receiving tertiary care at a hospital lipid clinic. PATIENTS: Subjects with severe primary hypercholesterolaemia (types IIa and IIb), already stabilised on a cholesterol-lowering diet, with serum cholesterol levels of 7.0 mmol/L or more and triglyceride levels of 6.0 mmol/L or less. Sixty-four subjects were randomly assigned to the treatment groups; three withdrew before any outcome observations; 61 completed the trial and their results were analysed. INTERVENTIONS: Subjects were randomly assigned to receive either colestipol placebo or colestipol 5 g or 10 g each morning in fixed dosage for 18 weeks. They simultaneously received incremental doses of simvastatin: placebo for six weeks, then 20 mg/night for six weeks, then 40 mg/night for a final six weeks. MAIN OUTCOME MEASURES: Lipids, lipoproteins, and haematological and biochemical safety parameters were measured at the end of each treatment period. Adverse events were monitored. RESULTS: Respective maximum reductions (95% confidence intervals) in serum cholesterol, LDL cholesterol and apolipoprotein B (apo-B) values in subjects taking combination therapy were 41% (38%-45%), 50% (46%-53%) and 43% (39%-46%), compared with lesser reductions of 32% (26%-37%), 38% (31%-45%) and 37% (32%-41%) in those taking simvastatin monotherapy. The percentage changes in LDL cholesterol with combination therapy were independent of baseline cholesterol level or lipid phenotype. Combination therapy reduced serum triglyceride levels by up to 24% (15%-32%) and increased high-density lipoprotein (HDL) cholesterol levels by up to 9% (3%-15%). Three subjects withdrew within a few weeks because of severe gastrointestinal side effects related to colestipol; 19 experienced milder gastrointestinal side effects, 15 were taking combination therapy. CONCLUSIONS: A combination of low-dose colestipol and simvastatin was found to be more effective in reducing serum and LDL cholesterol than simvastatin used alone. Such combination therapy offers the possibility of improved cholesterol lowering without the need for full dosage of either drug.

Anticholesteremic Agents↗
PubMed1992

Multiple medication use in the elderly. Use of prescription and non-prescription drugs in an Australian community setting.

OBJECTIVE: To document the extent of polypharmacy or multiple medication use in the elderly. DESIGN: Cross-sectional examination of an age cohort of a community. SETTING: Community-based study in Dubbo, NSW, in 1988-1989. SUBJECTS: All non-institutionalised residents aged 60 years and over, numbering 1237 men and 1568 women. MAIN OUTCOME MEASURES: Assessment of use of prescription and non-prescription drugs, recent hospitalisation, years of education, psychosocial variables. RESULTS: 18% of men and 25% of women were currently using three or more classes of prescription drugs. The corresponding values for two or more classes of non-prescription drugs were 29% and 44%. Of those who were using multiple prescription drugs 56% of men and 76% of women were also using multiple non-prescription drugs. In a multiple logistic model, the following possible predictors of multiple drug use were included: hospitalisation in the last six months, age, sex, depression, life satisfaction and education. Multiple prescription drug use was significantly predicted by recent hospitalisation (odds ratio [OR] = 2.40; 95% confidence interval [CI], 1.63-3.56), increasing age (e.g. 70-79 years versus 60-69 years; OR = 2.54; CI, 1.97-3.25), female sex (OR = 1.59; CI, 1.25-2.01) and increasing depression (e.g. highest tertile of depression scale versus lowest; OR = 2.52; CI, 1.84-3.42). Multiple non-prescription drug use was significantly predicted by female sex (OR = 2.38; CI, 1.95-2.92) and increasing depression (OR = 2.77; CI, 2.16-3.56). For prescription items, non-prescription items, and both categories in combination levels of use 20% above the population average have been documented. CONCLUSIONS: Polypharmacy in the elderly population appears to be predicted by recent hospitalisation, increasing age, female sex and increasing depression. There is potential for drug-drug interaction to occur, but the findings suggest target areas for preventive action.

Aged↗
PubMed1992

Health status and lifestyle in elderly Hawaii Japanese and Australian men. Exploring known differences in longevity.

OBJECTIVE: To contrast health status and lifestyle in two elderly populations with differing longevity. DESIGN: Comparison of two cross-sectional data sets. SETTING: Non-institutionalised subjects. SUBJECTS: Men aged 60-81 years resident in Dubbo, New South Wales (n = 1183, 1988-1989) and Japanese men of the same ages resident in Hawaii (n = 1376, 1980-1982). MAIN OUTCOME MEASURES: Cardiovascular and non-cardiovascular disease prevalence, risk factors, social and health status. RESULTS: A history of heart attack, angina and stroke was twice as prevalent in Dubbo men as in Hawaii Japanese. Other diseases were many times more prevalent in Dubbo--liver disease sixfold, prostate and renal disease twofold, and arthritis 1.5-fold. Hypercholesterolaemia and untreated hypertension were more prevalent in Dubbo (threefold and 1.5-fold respectively). Current smoking was similar in both groups, while diabetes was twice as prevalent in the Hawaii Japanese. More Dubbo men were widowed or lived alone, and fewer remained in paid employment. Dubbo men had more limited physical mobility. CONCLUSIONS: Elderly Dubbo men have an excess of cardiovascular disease and associated risk factors, as well as an excess of non-cardiovascular disease, compared with Hawaii Japanese. This may account, in part, for a higher total mortality rate in elderly Australians compared with Japanese. Some of this disease burden may be amenable to risk factor intervention.

Aged↗
PubMed1992

Dubbo Study of the elderly: hypertension and lipid levels.

Untreated hypertension in age groups below 60 years has been shown to be associated with significant elevations in serum cholesterol and triglyceride levels. Drug therapy of hypertension has also been shown to have adverse effects on lipoproteins. We have investigated lipid and lipoprotein levels in a community-based sample of men and women 60 years and older belonging to one of the following groupings: (a) normal blood pressure (n = 1075); (b) untreated hypertension (n = 329); (c) drug-treated hypertension (n = 880). Serum lipid, lipoprotein, apolipoprotein or plasma glucose levels did not vary significantly between untreated hypertensives and normotensives of either sex. In a multiple regression model controlling for possible influences of age, overweight, alcohol and tobacco usage, and presence of coronary heart disease, anti-hypertensive drug therapy significantly predicted increased serum triglycerides (P less than 0.001) and reduced high density lipoprotein (HDL) cholesterol levels (P less than 0.01) in both sexes, reduced apolipoprotein A-I levels in males (P less than 0.001), and increased apolipoprotein B (P less than 0.01) and plasma glucose levels (P less than 0.001) in females. Adjusted triglycerides were 20% higher and HDL cholesterol was 7% lower in the presence of anti-hypertensive drug therapy. These effects were partially consistent with the known actions of thiazide diuretics and beta-blockers which were used by more than 50% and 40% of subjects, respectively.

Adrenergic beta-Antagonists↗
PubMed1992

Lipoprotein(a) levels in chronic renal disease states, dialysis and transplantation.

Lipoprotein(a) is an independent risk factor for cardiovascular disease. Lipoprotein(a) levels were measured in 196 patients (103 Male [M]: 93 Female [F]) with chronic renal diseases and in 116 controls. Median levels of Lipoprotein(a) [Lp(a)] were found to be significantly elevated in patients with untreated chronic renal disease (285,285 mg/L; M,F; range 30-1675 mg/L) and in those treated with continuous ambulatory peritoneal dialysis (320, 603; M,F; range 50-1450) compared with controls (70,51; M,F; range 1-750; p less than 0.01 Males, p less than 0.001 Females). Lp(a) levels in patients treated by haemodialysis (133,35; M,F; range 5-685) and renal transplantation (100,95; M,F; range 10-1700) were not significantly different from controls. Lipoprotein(a) levels correlated inversely with serum albumin in the combined dialysis group (r = -0.34, p less than 0.001), and with urinary protein loss in the combined transplant and chronic renal diseases groups (r = 0.29, p less than 0.01). This correlation of Lp(a) with protein metabolism suggests a similarity with changes in other apolipoprotein-B containing lipoproteins in nephrosis. These findings may be relevant to the increased risk of atherosclerosis in patients with chronic renal disease and to their optimum mode of renal replacement therapy.

Aged↗
PubMed1992

Lipoprotein(a) concentration in diabetes: relationship to proteinuria and diabetes control.

Diabetic patients are at increased risk of cardiovascular disease, particularly when proteinuria is present. Lipoprotein(a)[Lp(a)] levels were assessed in 37 patients with insulin dependent (IDDM) and in 75 patients with non-insulin dependent (NIDDM) diabetes who showed varying degrees of proteinuria and glycaemic control. Median Lp(a) in 112 diabetic patients was significantly greater than in 116 healthy controls (113 vs 48 mg/L; p less than 0.01). 86 of the patients had first morning urine albumin concentration less than 30 mg/L (normoalbuminuria = NA), 16 patients 30-200 mg/L (microalbuminuria = MA) and ten patients greater than 200 mg/L (albuminuria = ALB). There was no significant difference in median Lp(a) concentration between the three groups (NA = 108, MA = 163, ALB = 98 mg/L; p greater than 0.5). No significant difference in median Lp(a) or NIDDM treated with oral agents and/or diet (120, 98, 115 mg/L respectively; p greater than 0.7). When the 86 NA patients were divided on the basis of median fructosamine concentration (357 mumol/L), no significant difference was found in median Lp(a) levels between those grouped below or above this median (98 mg/L vs 118 mg/L; p greater than 0.5). Across all diabetics studied there was no significant correlation present between Lp(a) and urinary protein or glycaemic control. These cross-sectional results suggest that median Lp(a) concentration is increased in both IDDM and NIDDM patients, but this increase is not related to the degree of proteinuria or short-term glycaemic control.

Adolescent↗
PubMed1991

Coronary risk factors six to twelve months after coronary artery bypass surgery. 1986 compared with 1990.

A 1986 study found that coronary risk factors were receiving insufficient attention in patients who had recently undergone coronary artery bypass grafting. This issue was readdressed in a like group of 100 patients from the same surgical unit three and a half years later, in 1990, to ascertain whether risk factor management had improved over the period. An increased proportion of patients in 1990 were undergoing active management of hypertension and hyperlipidaemia. Only 25% of patients in 1990 manifested hypercholesterolaemia (cholesterol levels greater than or equal to 6.5 mmol/L) compared with 60% in 1986. Five per cent of patients in 1990 manifested diastolic hypertension (diastolic pressure greater than or equal to 95 mmHg) compared with 23% in 1986. Such patients appear better managed in 1990 than they were in 1986.

Adult↗
PubMed1991

Dubbo study of the elderly: sociological and cardiovascular risk factors at entry.

A prospective study of elderly Australians commenced in 1988 in Dubbo, NSW. Its goals are to identify predictors of mortality, hospitalisation and placement in long-term care, with special focus on risk factors for cardiovascular disease. The study population were non-institutionalised subjects, comprising 1237 males and 1568 females 60 years and over. This report describes the baseline findings: demographic, educational and economic data; tobacco and alcohol usage, self-medication and other habits; medical contacts and past diagnosis; prescribed medication and in study diagnosis; psychosocial variables, functional health and social support; blood lipid and lipoprotein data; blood pressure, spirometry and glucose data; heights and weights. Where comparison has been feasible, the findings in Dubbo closely resemble those obtained from the rest of Australia. The findings presented provide the basis for aetiological studies of future outcomes.

Aged↗
PubMed1991

High density lipoproteins, genetic polymorphism for apo A-I and coronary artery disease.

HDL cholesterol and apolipoprotein A-I are associated with the development of coronary artery disease (CAD). The presence of a PstI site polymorphism adjacent to the gene encoding apo A-I (known as P2) has also been shown to be associated with CAD but this relationship is controversial. A case control study was conducted in an Australian population to re-examine whether the rare P2 allele is associated with CAD. Data were derived from 159 cases of angiographically confirmed CAD and 99 healthy controls. The proportion of CAD cases carrying the P2 allele did not differ significantly from controls (11% versus 9%). In a multiple logistic regression model controlling for the effects of age, country of birth, hypertension and hypotensive drugs, body mass index and lipid variables, the P2 allele failed to predict significantly the presence of CAD (odds ratio 1.83; 95% confidence interval 0.65-5.19).

Alleles↗
PubMed1991

The Dubbo study of the health of elderly: correlates of coronary heart disease at study entry.

A prospective study of the health of elderly Australians recently commenced in Dubbo, NSW, the study population comprising 1,237 males and 1,568 females 60 years and older. The prevalence rates of coronary heart disease (CHD) and its associated risk factors have been examined in the baseline data. The age-standardized rate of CHD was 23.8/100 in males and 18.1/100 in females. The prevalence rate increased with age until 79 years in males, thereafter declining. The rate increased steadily with age in females. In a multiple logistic model, the following possible predictors of CHD were included: age, cigarette smoking, use of alcohol, exercise, religiosity, years of education, hypertension, diabetes, family history of CHD, body mass index, lipid and lipoprotein variables. The presence of CHD in males was significantly predicted by age, hypertension (odds ratio, OR = 1.40), family history (OR = 2.05), and high density lipoprotein (HDL) cholesterol (OR = 0.78). The significant predictors in females were age, years of education (OR = 0.82), hypertension (OR = 1.45), family history (OR = 1.77), serum triglycerides (OR = 1.30), and HDL cholesterol (OR = 0.73). Hypertension was found to be a stronger predictor of CHD in the younger age group (60-69 years), while diabetes was a predictor of CHD in older males (70-79 years). Our findings require confirmation in the prospective study now in progress.

Age Factors↗
PubMed1990

Comparison of simvastatin and cholestyramine in the treatment of primary hypercholesterolaemia.

The effects of simvastatin, a competitive inhibitor of the enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase, on plasma lipid levels were compared with those of the bile acid sequestrant cholestyramine in a randomized parallel study of 60 subjects with primary hypercholesterolaemia. After a 12-week direct comparison period 37 subjects with inadequate cholesterol reduction received a combination of both drugs and all subjects were followed for a further 40 weeks. Simvastatin was more effective than cholestyramine in lowering total and LDL cholesterol levels and the LDL/HDL ratio (-31.7% v. -19.7% [P less than 0.01], -41.0% v. -31.8% [P less than 0.05] and -46.7% v. -33.6% [P less than 0.01], respectively at Week 12). Only simvastatin significantly increased the HDL cholesterol concentration (+13.3% [P less than 0.01] v. +6.4%). Cholestyramine increased plasma triglyceride levels by 37.5% (P less than 0.01) whereas simvastatin caused a slight non-significant reduction. Combined therapy produced a further decrease in total and LDL cholesterol levels, and in the LDL/HDL ratio, which was sustained for the duration of the study. Simvastatin was better tolerated than cholestyramine (P less than 0.01), and combining the two drugs enhanced efficacy without increasing the frequency of side effects.

Adult↗
PubMed1990

On the mechanism by which an ACAT inhibitor (CL 277,082) influences plasma lipoproteins in the rat.

CL 277,082 is an inhibitor of acyl-CoA: cholesterol acyltransferase (ACAT). The effects of this drug on lipoprotein metabolism have been examined in cholesterol-fed rats. An optimal dose of drug incorporated into the diet (0.1% w/w) for 7 days reduced plasma cholesterol by 48% and plasma triglycerides by 72%. The decrease in plasma cholesterol was due to a reduction in triglyceride-rich lipoproteins and in HDL cholesterol. There was a significant 72% reduction in intestinal ACAT activity, accompanied by a 41% reduction in hepatic cholesterol content. There was a smaller 21% reduction in hepatic ACAT activity. Hepatic HMG-CoA reductase activity increased 3-fold. HDL binding activity by liver membranes was not altered significantly. The decrease in plasma cholesterol with this ACAT inhibitor is most likely due to decreased absorption of dietary cholesterol resulting from inhibition of intestinal ACAT.

Analysis of Variance↗
PubMed1990

Effects of an ethyl ester preparation of fish oils (Himega) on lipids and lipoproteins in hyperlipidaemia.

Clinical trials were conducted to assess the utility of HimegaR in the management of hyperlipidaemia. Himega is an ethyl ester concentrate from fish oil containing at least 50% n-3 fatty acid and minimal cholesterol. In Study 1, 13 subjects with primary hypertriglyceridaemia consumed Himega or a triglyceride-based fish oil in a randomised, double-blind crossover study for 12 weeks. Nine subjects took 2 g/day of n-3 fatty acid but four subjects with marked hypertriglyceridaemia took 4 g/day. Plasma triglycerides were reduced by approximately 50% with either product. There was a very similar effect on all lipid and lipoprotein parameters, including an 18% increase in LDL cholesterol and 23% increase in serum apolipoprotein B. In Study 2, nine subjects with primary hypercholesterolaemia took 2 g/day of n-3 fatty acid (Himega) or placebo (olive oil) in a randomised, double-blind crossover study for nine weeks. Plasma cholesterol was reduced by 6%, without significant change in LDL cholesterol. Fish oils in the form of ethyl esters or triglyceride are assimilated to a similar degree and lead to equivalent triglyceride-lowering in hypertriglyceridaemia, while simultaneously increasing LDL particle numbers. Himega does not reduce LDL levels in hypercholesteraemia, despite being a product with minimal cholesterol content.

Adult↗
PubMed1990

The Dubbo study: an Australian prospective community study of the health of elderly.

The proportion of Australian population over 60 years has risen progressively over the last 40 years and this growth is projected to continue. Major health problems of the elderly include coronary heart disease, cerebro-vascular disease, osteoporosis and fracture. The risk factors for coronary heart disease and stroke in middle-aged subjects have been extensively documented in prospective studies in Australia and elsewhere, and include lipid disorders, hypertension, cigarette smoking, diabetes and family history. Few prospective studies have been targeted exclusively on the elderly and information available with respect to vascular risk factors is fragmentary and contradictory. This is the background to a new prospective study of the health of elderly Australians now under way in Dubbo, NSW. The goals of the Dubbo Study are to identify predictors of mortality, hospitalisation and placement in long-term care, while specific aims are the study of risk factors for chronic diseases and disability. This report describes the study rationale, reasons for selecting Dubbo as the study site, methods and measures, participation rates and demography. The target population included all non-institutionalised subjects 60 years and over, domiciled in Dubbo, and is comprised of 1693 males and 2167 females. The attendance rate for an extensive medical and sociological baseline assessment over a 13 months' period was 73% for both sexes. The prospective study is now in place and within three to five years will be generating definitive information in the elderly.

Aged↗