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Biomedical subjects

L A Simons

Publications and source records attributed to L A Simons.

At least 37 records · Page 2Linked to original sources
PubMed1997

Relationship of peak expiratory flow rate with mortality and ischaemic heart disease in elderly Australians.

OBJECTIVE: To evaluate the relationships of mortality and ischaemic heart disease (IHD) with peak expiratory flow rate (PEF) in the elderly. DESIGN: Prospective study with median follow-up of 83 months. SETTING: Dubbo, a New South Wales country town (population, 30500). SUBJECTS: Non-institutionalised residents born before 1930 (i.e., aged 60 years and over at study entry). Participation rate was 73% (1235 men and 1570 women). MAIN OUTCOME MEASURES: Baseline demographic, psychosocial and standard cardiovascular risk factors, including PEF; all-causes mortality, IHD mortality and IHD events (hospitalisations with any manifestation of IHD) by tertile of PEF. RESULTS: More subjects with PEF in the lowest tertile (I) had a past history of respiratory disease, were current cigarette smokers and were taking antihypertensive drugs. During follow-up, 321 men (26%) and 252 women (16%) died. All-causes mortality was three (men) to four (women) times higher for those in PEF tertile I than for those in tertile III. IHD mortality and IHD events showed similar trends. In a proportional hazards model adjusted for age, height, smoking status and other risk factors or confounders, the hazard ratios (95% confidence interval) for men in PEF tertile I versus tertile III were: all-causes mortality, 1.62 (1.14-2.30); IHD mortality, 1.75 (0.96-3.20); and IHD events, 1.12 (0.82-1.53). For women, respective hazard ratios were 1.92 (1.23-3.00), 2.58 (1.24-5.39), and 1.16 (0.83-1.63). CONCLUSIONS: We confirm an independent, inverse relationship between PEF and all-causes and IHD mortality. The data suggest a potential benefit for coronary risk factor management in subjects with existing airways disease and further support the case for antismoking programs.

Aged↗
PubMed1996

Apparent discontinuation rates in patients prescribed lipid-lowering drugs.

OBJECTIVE: To evaluate apparent discontinuation rates in patients newly prescribed lipid-lowering drugs. DESIGN AND SETTING: A prospective survey of 12 months' dispensing data in 138 community pharmacies across metropolitan Sydney. PATIENTS: 610 adults (49% men) with a mean age of 58 years; 91% of prescriptions were from general practitioners; prescribed drugs were simvastatin (54%), pravastatin (31%) and gemfibrozil (15%). MAIN OUTCOME MEASURE: The number of patients failing to collect prescription refills. RESULTS: 60% of patients (95% confidence interval [CI], 56%-64%) apparently discontinued their medication over 12 months. Half of the apparent discontinuations occurred within three months and a quarter within one month of starting treatment. The predominant reasons for discontinuation were: patient unconvinced about need for treatment (32%), poor efficacy (32%) and adverse events (7%). Only half of those experiencing poor efficacy were switched to another drug. The relative risk (RR) of discontinuation was lower in older patients (age 65+ v. <50 years: RR 0.66; 95% CI 0.47-0.93) and in those using other cardiovascular drugs (RR 0.69; CI 0.56-0.86), but was increased in those showing early evidence of poor compliance (RR 1.77; CI 1.33-2.35). Discontinuation appeared to be unrelated to sex, the source of the prescription (general practitioner or specialist), past use of lipid-lowering drugs or the cost of medication. CONCLUSIONS: High apparent discontinuation rates with lipid-lowering drugs suggest significant wastage of resources in treatments that are initiated but not continued and a lost opportunity for heart disease prevention. Many patients appear to discontinue therapy for illogical reasons and this may be amenable to intervention.

Aged↗
PubMed1996

M235-->T polymorphism of the angiotensinogen gene predicts hypertension in the elderly.

OBJECTIVE: To determine whether the M235-->T polymorphism (exon 2) of the angiotensinogen gene is associated with hypertension in elderly patients with isolated systolic hypertension [ISH: systolic blood pressure (SBP) > or = 160 mmHg, diastolic blood pressure (DBP) < 90 mmHg) or systolic-diastolic hypertension (SDH: DBP > or = 90 mmHg, SBP > or = 160 mmHg) compared with normotensive controls (SBP < 160 mmHg, DBP < 90 mmHg). DESIGN: A case-control study in 769 non-institutionalized, elderly (aged > or = 60 years; female:male ratio 0.85) residents of Dubbo, New South Wales. METHODS: Individuals were classified as having ISH (n = 171), having SDH (n = 218) and being normotensive controls (n = 366) with age and sex matching. MM, TT and MT genotypes were determined by a nested polymerase chain reaction strategy using DNA extracted from serum. The prediction of ISH or SDH by genotype or allele was examined in a multiple-logistic regression model that controlled for various confounders. RESULTS: SBP (mean +/- SD, mmHg)/DBP (mean +/- SD, mmHg) was 176 +/- 16/79 +/- 8 in the ISH group, 167 +/- 23/97 +/- 7 in the SDH group and 134 +/- 14/74 +/- 9 in the normotensive control group. The frequencies of M and T alleles in the normal population (0.69 and 0.31, respectively) were altered significantly in the ISH group (0.61 and 0.39, respectively; chi 2 = 6.0, P < 0.02) and the SDH group (0.62 and 0.38, respectively; chi 2 = 6.0, P < 0.02). The presence of the TT genotype predicted both ISH (odds ratio 1.9, 95% confidence interval 1.1-3.3) and SDH (1.7, 1.0-3.0) as did that of the T allele (ISH: 1.3, 1.0-1.7; SDH: 1.3, 1.0-1.7). CONCLUSIONS: The M235-->T polymorphism may be a marker for both forms of hypertension in the elderly. Whether the TT genotype represents a genetic risk factor for the development of hypertension in later life requires confirmation.

Aged↗
PubMed1996

What dose of vitamin E is required to reduce susceptibility of LDL to oxidation?

BACKGROUND: Oxidation modification of low density lipoprotein (LDL) may play a role in the pathogenesis of atherosclerosis. Ingestion of vitamin E in high dosage has been shown to reduce the susceptibility of LDL to copper-induced oxidation, as assessed ex vivo. AIM: To determine a minimum dose of supplementary vitamin E which will significantly reduce the susceptibility of LDL to oxidation. METHODS: A single centre, double-blind, parallel placebo-controlled trial. Healthy volunteers (total n = 42) were randomised to receive placebo, 500, 1000 or 1500 IU/day of vitamin E (D-alpha-tocopherol) for a period of six weeks. Primary outcomes were change in lag time or oxidation rate to copper-induced LDL oxidation. Secondary outcomes were changes in plasma vitamin E levels and clinical tolerance. RESULTS: Lag time to LDL oxidation was significantly prolonged and oxidation rate significantly slowed at all dose levels of vitamin E, indicating a threshold effect from 500 IU/day. Compared to placebo, the median prolongation in lag time on 500 IU/day was 26%, on 1000 IU/day 24% and on 1500 IU/day 35%. The corresponding slowing in oxidation rates was 14%, 19% and 25% respectively. The per cent change in plasma vitamin E concentration was highly correlated with the change in lag time (r = 0.61, p < 0.001) and oxidation rate (r = 0.55, p < 0.001). Vitamin E was generally well tolerated. CONCLUSIONS: Vitamin E in a dose of 500 IU/day will significantly reduce the susceptibility of LDL to oxidation. Whether or not this treatment will consistently reduce the future incidence of coronary artery disease will only be answered by further clinical trials.

Analysis of Variance↗
PubMed1996

Predictors of mortality in the prospective Dubbo study of Australian elderly.

BACKGROUND: A prospective study in non-institutionalised Australian elderly 60 years and over commenced in Dubbo, NSW in 1988. AIM: To examine clinical and socio-demographic predictors of all-causes mortality. METHODS: The data were derived from a community-based sample comprising 1236 men and 1569 women followed for a median period of 62 months. RESULTS: Two hundred and thirty five men (19%) and 184 women (12%) died, 46% of male and 53% of female deaths respectively related to cardiovascular disease. In a proportional hazards model, the significant predictors of mortality were: older age, being married (relative risk [RR] = 0.71 for men, 0.74 for women), current smoking for men (RR = 3.11), taking more than three alcoholic drinks per day for men (RR = 0.37), prior coronary heart disease for men (RR = 1.36), severe hypertension for women (RR = 1.99), use of anti-hypertensive medication for men (RR = 1.74), diabetes for men (RR = 1.62), poor-fair self-rated health for women (RR = 1.74) and physical disability for men (RR = 1.72). Serum cholesterol was associated with mortality in a 'J-shaped' relationship in men and in a reciprocal relationship in women. Blood pressure predicted mortality in an incremental fashion below 75 years, but in older subjects lower pressure was associated with excess mortality. CONCLUSION: Some predictors of mortality in the well elderly have been identified and a more extended period of follow-up will possibly resolve contradictory findings in some areas.

Aged↗
PubMed1996

Diabetes, mortality and coronary heart disease in the prospective Dubbo study of Australian elderly.

BACKGROUND: A prospective study of Australian elderly living in Dubbo has shown that diabetes is a significant predictor of all-causes mortality and coronary heart disease (CHD). AIM: To examine and contrast clinical and socio-demographic predictors of these outcomes in those with and without diabetes. METHODS: The data are derived from a community-based sample of subjects 60 years and older followed over 62 months since 1988. Of 1155 men and 1472 women, 9.2% and 6.9% respectively manifested diabetes at baseline, based on history or fasting hyperglycaemia. RESULTS: In the presence of diabetes, all-causes mortality was increased twofold in both sexes, CHD incidence was increased twofold in men and threefold in women, stroke incidence was increased twofold in women but little changed in men. Proportional hazards models were derived separately for persons with and without diabetes and risk factors differentially predictive in diabetes were sought. Significant predictors of death in diabetes were old age and current smoking. Those factors differentially predictive were 'being married' (Relative Risk [RR] 1.60 with diabetes and 0.69 without diabetes) and higher body mass index (BMI) (RR 1.03 with diabetes and 0.79 without diabetes). Significant predictors of CHD in diabetes were old age, prior CHD, severe hypertension, low HDL cholesterol and self-rated health. Those factors differentially predictive were higher body mass index (RR 1.14 vs 0.83) and physical disability (RR 0.69 vs 1.55). Differential predictions with regard to BMI may relate in part to excess CHD and mortality at low BMI in non-diabetic subjects. CONCLUSION: The vascular disease burden of diabetes in the elderly has been confirmed, especially in women. A number of conventional risk factors are contributing to this burden and may be amenable to treatment.

Aged↗
PubMed1996

Alcohol intake and survival in the elderly: a 77 month follow-up in the Dubbo study.

BACKGROUND: A prospective study in non-institutionalised Australian elderly aged 60 years and over commenced in Dubbo, NSW in 1988. AIM: To examine the relationship between all-causes mortality and alcohol intake. METHODS: The data were derived from a community-based sample comprising 1236 men and 1569 women followed for a median period of 77 months. Regular alcohol intake was reported by 78% of men and 52% of women. Eighty-seven per cent of men and 44% of women primarily drank beer. RESULTS: Death occurred in 305 men and 236 women, 34% and 39% respectively from coronary heart disease (CHD). In a proportional hazards model, the hazard ratio (HR) for all-causes mortality in male drinkers, compared with abstainers, was 0.75 at one-seven drinks/week, 0.76 at eight-14 drinks/week, 0.69 at 15-28 drinks/week and 0.49 at > 28 drinks/week (p < 0.04), an inverse relationship. In female drinkers, HR was 0.78 at one-seven drinks/week, 0.49 at eight-14 drinks/week (p < 0.04) and 0.62 at 15-28 drinks/weeks, potentially a U shaped relationship. The effect on all-causes mortality could not be attributed to a differential effect of beer versus wine/spirit intake. Although the mortality rate was lower in those taking any alcohol compared with abstainers, those taking any alcohol exhibited an increased proportion of deaths due to cancer at the expense of a reduced proportion of CHD and stroke deaths. CONCLUSIONS: Alcohol intake in the Dubbo elderly appears to be independently associated with a significant increase in life expectancy. Mechanisms underlying the effect may emerge at a longer interval of follow-up.

Aged↗
PubMed1996

I/D polymorphism of the angiotensin-converting enzyme gene does not predict isolated systolic or systolic-diastolic hypertension in the elderly.

To determine whether insertion/deletion (I/D) polymorphism (intron 16) of the angiotensin converting-enzyme (ACE) gene is associated with isolated systolic hypertension (ISH: systolic blood pressure (BP) > or = 160, diastolic BP < 90 mm Hg) or systolic-diastolic hypertension (S-D hypertension: diastolic BP > or = 90 +/- systolic BP > or = 160 mm Hg) compared with normotensive controls (systolic BP < 160, diastolic BP < 90 mm Hg), we conducted a case-control study of 733 non-institutionalised, elderly (> or = 60 years) residents of Dubbo, NSW. Individuals were classified as: ISH (n = 167), S-D hypertension (n = 207) and normotensive control (n = 359) with age and sex matching. II, DD and ID genotypes were determined by a nested PCR strategy using DNA extracted from serum. The frequencies of D and I alleles in the control population (0.70 and 0.30 respectively) were not significantly different in the ISH group or the S-D hypertension group (chi 2: 1.7, P = 0.42). After adjustment for several potential confounders, neither genotype nor allele predicted ISH (II vs DD: odds ratio (OR): 1.06, 95% confidence interval (CI): 0.55-2.03; I vs D: 1.09, 0.82-1.46) or S-D hypertension (II vs DD: 1.19, 0.67-2.10; I vs D: 1.16, 0.89-1.52) in this elderly cohort. The I/D polymorphism of the ACE gene is not a marker for either form of hypertension in this large elderly sample.

Aged↗
PubMed1996

Treatment of lipids. Implications for the general practitioner.

Abnormalities in serum lipids are important predictors of coronary artery disease. Lipid therapy safely reduces the future risk of coronary disease and simultaneously improves life expectancy. These benefits have been demonstrated in patients with and without-prior heart disease. Lipid therapy needs to be prioritized for those at highest absolute risk of coronary disease, that is, in those with established coronary disease or in those with other major risk factors such as diabetes, a positive family history of coronary disease, low high density lipoprotein (HDL) cholesterol level, hypertension or cigarette smoking. Drug selection is discussed, as is the place of lipid therapy in the elderly. Many patients fail to continue their lipid therapy beyond a few weeks and this problem needs to be considered by the general practitioner.

Family Practice↗
PubMed1995

On the effect of garlic on plasma lipids and lipoproteins in mild hypercholesterolaemia.

The ingestion of garlic has been reported to have many cardiovascular effects, including a reduction in plasma cholesterol concentration and the susceptibility of LDL to oxidation. A double-blind, placebo-controlled, randomised crossover study was conducted in subjects with mild to moderate hypercholesterolaemia who were subject to strict dietary supervision and assessment. After a baseline dietary period of 28 days, subjects took Kwai garlic powder tablets 300 mg three times daily or matching placebo for 12 weeks, followed by 28 days washout, followed by a 12 weeks crossover on the alternative preparation. In the analysis hypercholesterolaemia was defined as those subjects in the range 5.5-8.05 mmol/l. Three subjects were withdrawn, one allocated to garlic and complaining of garlic body odour, one using placebo having intercurrent health problems, and one with a baseline cholesterol below 5.5 mmol/l, yielding analysable results in 28 subjects. Comparing the period on garlic with that on placebo, there were no significant differences in plasma cholesterol, LDL cholesterol, HDL cholesterol, plasma triglycerides, lipoprotein(a) concentrations, or blood pressure. Mean LDL cholesterol concentration was 4.64 +/- 0.52 mmol/l on garlic and 4.60 +/- 0.59 mmol/l on placebo. There was no demonstrable effect of garlic on oxidisability of LDL, on the ratio of plasma lathosterol/cholesterol (a measure of cholesterol synthesis), nor on LDL receptor expression in lymphocytes. This study found no demonstrable effect of garlic ingestion on lipids and lipoproteins.

Administration, Oral↗
PubMed1995

Risk factors for coronary heart disease in the prospective Dubbo Study of Australian elderly.

A new prospective study of non-institutionalised Australian elderly 60 years and over commenced in Dubbo in 1988, comprising 1236 men and 1569 women. This report examines clinical and socio-demographic predictors of coronary heart disease (CHD) over a median 62 months follow-up. CHD incidence rates (ICD-9-CM codes 410-414) were higher in men than women until 79 years, thereafter, the rates for recurrent disease were higher in women. Incidence rates for recurrent disease were three-fold those for initial disease. In Cox proportional hazards analysis, the significant predictors of all CHD were: advancing age, prior CHD (relative risk (RR) = 2.50 and 2.15 in men and women, respectively), use of anti-hypertensive medication (RR = 1.92 and 1.75 in men and women, respectively). diabetes (RR = 1.67 and 1.53 in men and women, respectively), serum cholesterol, low density lipoprotein cholesterol and serum apo B in men (RR = 1.24), serum triglycerides in women (RR = 1.23), high density lipoprotein cholesterol in men (RR = 0.82), lipoprotein (a) in women (RR = 1.99), and poorer self-rating of health (RR =1.48 and 1.93 in men and women, respectively). Serum cholesterol was not predictive of CHD in men beyond 74 years. Isolated systolic hypertension predicted CHD in women (RR = 3.76), but not in men (RR = 1.20). The findings highlight key risk factors for CHD in the elderly.

Aged↗
PubMed1994

Coronary risk factors 6-12 months after coronary artery bypass grafting. Comparison of surveys in 1986, 1990 and 1994.

OBJECTIVE: To assess coronary risk factors and management 6-12 months after coronary artery bypass grafting. DESIGN: Patient survey by questionnaire after discharge from hospital in 1994 and comparison with similar surveys from 1990 and 1986. SETTING AND PATIENTS: One hundred and ninety-four patients undergoing coronary artery bypass grafting at one hospital campus between 1 March 1993 and 31 August 1993. Replies to questionnaires were received from 175 patients (90%); we had clinical and biochemical data for 166-175 patients (86%-90%). RESULTS: The proportion with hypercholesterolaemia (serum cholesterol levels > or = 6.5 mmol/L) declined from 60% in 1986 to 9% in 1994. Those with diastolic hypertension (> or = 95 mmHg) declined from 23% to 3%. The proportion of current smokers remained low at 6%. The proportion overweight had increased from 32% in 1986 to 47% in 1994. The proportion taking lipid-regulating drugs increased from 2% in 1986 to 37% in 1994. CONCLUSION: Coronary risk factors after coronary artery bypass grafting appear to be better managed in 1994 than in earlier years, but there may still be a need for improvement in lipid disorders and weight.

Adult↗
PubMed1994

FH-Sydney 1 and 2: two novel frameshift mutations in exon 10 of the low-density lipoprotein receptor gene detected by heteroduplex formation.

We report two novel frameshift mutations in exon 10 of the low-density lipoprotein receptor gene that lead to familial hypercholesterolemia in separate lineages. The lesions, FH-Sydney 1 and FH-Sydney 2, were detected by a modified heteroduplex analysis of exon-specific polymerase chain reaction (PCR) amplified DNA, and characterized at the molecular level by sequencing. Restriction enzyme digestion of PCR amplified DNA confirmed the presence of the mutant alleles in affected family members and their absence in nonaffected family members in both lineages. FH-Sydney 1 is a 4-bp duplication at position 1373, while FH-Sydney 2 is a 2-bp deletion at position 1478. The predicted result of both mutations is the premature truncation of the receptor at stop codons generated downstream of the mutations. Neither mutation was detected in a survey of 54 unrelated familial hypercholesterolemia patients.

Base Sequence↗
PubMed1994

Efficacy of drug intervention for lipids in the prevention of coronary artery disease.

Meta-analysis of the benefit of drug intervention in hypercholesterolaemia has produced conflicting conclusions, dependent upon which studies were included or which outcomes were considered. We have approached this question by considering coronary artery disease (CAD) outcomes, fatal and non-fatal, in studies considered to be pivotal--those of sufficient size and duration and those achieving sufficient cholesterol reduction to be likely to have a statistically significant outcome. In parallel, we have reviewed all the published angiographic trials of adequate design (randomised and controlled). In four pivotal primary prevention studies, CAD morbidity was reduced in the range 19-45%. CAD mortality was reduced significantly in one of these studies. Women were included in only one study and they did not exhibit the favourable outcome observed in men. In four pivotal secondary prevention studies, CAD morbidity was reduced in the range 5-36%. CAD mortality was significantly reduced in two studies. In eight angiographic intervention studies, lipid intervention was associated with consistently more evidence of regression or stable coronary disease. These studies also yielded suggestive evidence of improved clinical outcome. We conclude that drug intervention to lower cholesterol levels effectively reduces CAD morbidity and mortality in men already suffering from CAD (and may do so in women). Treatment is similarly effective in men with hypercholesterolaemia having no prior history of CAD. We lack evidence of the value of treatment in the elderly or in women having no prior CAD.

Anticholesteremic Agents↗
PubMed1993

The low-density lipoprotein receptor and cholesterol synthesis are affected differently by dietary cholesterol in the rat.

In the hamster and the rabbit, the low-density lipoprotein (LDL) receptor and cholesterol synthesis are coordinately downregulated by dietary cholesterol. In the rat, cholesterol synthesis is downregulated but LDL kinetic studies suggest that the LDL receptor is not. The aim of this study was to determine the effect of dietary cholesterol on the expression of the hepatic LDL receptor in the rat. Young (2 months) hooded and albino Wistar rats and older (9 months) Sprague-Dawley rats were used because of their reported different propensities to develop hypercholesterolaemia when fed cholesterol. Hepatic LDL receptor activity was measured using a dot blot assay with LDL-gold and LDL receptor mass was measured using an electroblot assay with a polyclonal antibody. Dietary cholesterol had no effect on the plasma cholesterol concentration in both strains of young Wistar rats but increased it in the older Sprague-Dawley rats. Cholesterol synthesis as measured with 3H2O or as indicated by 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity or the ratio of plasma lathosterol to cholesterol was effectively downregulated by dietary cholesterol (1% w/w) in all three strains. In contrast, dietary cholesterol increased both hepatic LDL receptor activity and mass in the young Wistar rats and had no effect on either receptor activity or mass in the older Sprague-Dawley rats. Increases in receptor activity occurred despite increases in hepatic cholesterol especially when cholic acid was added to the cholesterol diet. The effect was systemic because CL 277082, an inhibitor of intestinal cholesterol absorption, prevented the increase in LDL receptor activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗