Factors contributing to variation in lipoprotein (a) in Melbourne Anglo-Celtic population.

AIM: The purpose of this report is to survey the factors contributing to variation in lipoprotein(a) (Lp(a)) in a population-based sample of Anglo-Celtic Melburnians. RESULTS: The plasma Lp(a) levels were highly skewed towards low levels in this population, with a median of 156 mg/l and a mean of 262 mg/l. Approximately 33% had plasma Lp(a) above the threshold value of 300 mg/l, while 35% had Lp(a) levels below 100 mg/l. The most commonly occurring phenotype was apo(a) S3. In this phenotype, Lp(a) concentrations ranged from 10 to 596 mg/l. Lp(a) was consistently associated with diastolic blood pressure, systolic blood pressure, total protein, albumin and nitrogen excretion in the 40-60 y age group. Multiple stepwise regression analyses, in non-dietary factors, were used to explain about 13% of the variance in Lp(a) (19% in men and 23% in women). Remarkably, in the <40 y age group, non-dietary factors may account for 86% of the variance in Lp(a) and dietary factors, analysed separately, 46%. Thus, although Lp(a) is mainly genetically determined, there are clearly other factors which contribute to variations in Lp(a) concentrations.

Variability of standard clinical protein assays in the analysis of a model urine solution of fragmented albumin.

OBJECTIVES: This study investigates the sensitivity of various standard clinical techniques in the detection of albumin fragments. The significance of this work is in the detection of urinary proteins, such as albumin, which has recently been discovered to be excreted as mainly peptide fragments as a result of filtered albumin undergoing degradation during renal passage. All filtered proteins undergo a similar degradation process. DESIGN AND METHODS: Albumin digested with trypsin was used as a model urine solution. The solution was assayed for albumin concentration by various methods including the biuret assay that is known to detect urinary albumin fragments. The digest solution was also analyzed by various clinically used chromagen assays, electrophoretic and chromatographic methods to determine whether they are able to detect the fragmented protein. RESULTS: The benzethonium chloride, Coomassie blue, and pyrogallol red assays for urine protein, the immunoassay for human albumin and sodium dodecyl sulfate polyacrylamide gel electrophoresis with Coomassie blue staining were unable to detect the albumin fragments. Capillary electrophoresis was sensitive to the fragments but with low resolution. High-performance liquid chromatography gave the best results. CONCLUSIONS: Many techniques utilized to assay patient urine samples are unable to detect fragmented albumin and, hence, will severely underestimate albumin and protein excretion.

Plasma lipoprotein (a) concentrations and apolipoprotein (a) phenotypes in an Aboriginal population from Western Australia.

Factors contributing to the variation in plasma lipoprotein (a) (Lp(a)) concentration were surveyed in an Aboriginal population (175 men and 219 women), aged 24-86 years, from Western Australia. The plasma Lp(a) levels were highly skewed towards low levels in this population, with a median of 84 mg/L and a mean of 166 mg/L. Approximately 20% had plasma Lp(a) above the threshold value of 300 mg/L, while 52% had Lp(a) levels below 100 mg/L. The most commonly occurring phenotype was apolipoprotien(a) S4. In this phenotype, Lp(a) concentrations ranged from not detectable to 468 mg/L. There was a positive relationship between cigarette smoking and plasma Lp(a) concentration in men. Apolipoprotein A1 and bilirubin were positively associated with Lp(a) in the 40-60 age group and a positive relationship between weight and Lp(a) concentrations was observed in those aged 60 years or over. Thus, although Lp(a) is mainly genetically determined, there are clearly other factors which contribute to variations in Lp(a) concentrations.

Helicobacter pylori as a pathogenic factor in Ménétrier's disease.

The cause of Ménétrier's disease is unknown, although various autoimmune, allergic, and infective causes have been postulated. This case report describes a 37-yr-old man with Ménétrier's disease associated with protein-losing enteropathy and Helicobacter pylori infection. Clinical, endoscopic, histological, and biochemical resolution occurred after treatment of Helicobacter pylori infection. The improvement observed in this case supports an etiological role for H. pylori infection in Ménétrier's disease.

Cross-cultural comparison of Lp(a) profiles.

Lipoprotein(a) (Lp(a)) and apolipoprotein(a) (apo(a)) phenotypes as genetic markers for coronary heart disease (CHD) have been the focus of great interest in recent times. Included in this study were four Australian populations comprising 348 Anglo-Celtic Melburnians (157 men and 191 women), 339 Chinese Melburnians (169 men and 170 women), 402 South Asian Melburnians (216 men and 186 women) and 394 Aboriginal Australians from Western Australia (175 men and 219 women). Plasma Lp(a) concentrations were more highly skewed towards the lower range in the Chinese and Aboriginal groups than in the Anglo-Celtics and South Asians. Approximately 33% of Anglo-Celtics, 20% Aboriginals, 13% Chinese and 44% South Asians had plasma Lp(a) levels above the generally accepted risk threshold values of 300 mg/L. In Aboriginals and Chinese, the S4 apo(a) phenotype predominated while in Anglo-Celtics and South Asians, the highest frequency occurred in the S3 phenotype. In the S4 phenotype, Lp(a) values varied between the four populations but there was no significant difference in concentration between gender.

Platelet trans fatty acids in relation to angiographically assessed coronary artery disease.

Epidemiological and metabolic studies indicate that a higher intake of trans fatty acids (TFA) may be associated with increased risk of coronary heart disease (CHD). In a cross-sectional study of patients who underwent coronary angiography, the relationships between TFAs, measured in platelets, and the degree of coronary artery disease (CAD) were examined in 191 non-diabetic patients (134 men and 57 women). The degree of CAD was quantified by using an angiographic scoring system developed to provide an estimate of the extent of coronáry atherosclerosis: an "extent score'. The TFA composition of platelets, including palmitelaidic (16:1 omega 7t), elaidic (18:1 omega 9t), trans-10-octadecaenoic acid (18:1 omega 8t), trans vaccenic (18:1 omega 7t), trans-12-octadecaenoic acid (18:1 omega 6t) and linoelaidic (18:2 omega 6tt) acids, was measured by using gas chromatography and quantified as a percentage of total fatty acids. After adjustment for established CHD risk indicators, including age, gender, cigarette smoking, hypertension and serum total cholesterol concentration, elaidic acid (P = 0.0300) and trans-10-octadecaenoic acid (P = 0.0434) were positively associated with the extent score of CAD. The adjusted associations between other individual TFAs, including palmitelaidic acid (P = 0.1189), vaccenic acid (P = 0.7651), trans-12-octadecaenoic acid (P = 0.0582) and linoelaidic acid (P = 0.8793), and the extent score were not significant. The results of this study, therefore, provide evidence for an association between particular platelet TFAs and the degree of CAD in the patient population studied.

Coronary atherosclerosis in relation to body fatness and its distribution.

In a cross-sectional study of 226 patients (160 men and 66 women) who underwent coronary angiography, the relationships between total body fatness and abdominal fat distribution, and angiographically assessed coronary artery disease (CAD) were examined. Two different scoring systems were used to quantify the degree of CAD: an 'extent score' and a 'myocardial score'. The extent score provides an estimate of the extent of coronary atherosclerosis and the myocardial score provides an assessment of the amount of myocardium threatened by coronary lesions. Total body fatness was estimated using the body mass index (BMI) and the waist-to-hip circumference ratio (WHR) was used to assess abdominal fat distribution. The weight and height were obtained by questionnaire at the time of angiography, and self-reported waist and hip circumference measurements were used to calculate WHR. The BMI and WHR were associated with several coronary heart disease (CHD) risk factors. However, BMI was not significantly associated with either of the CAD scores. The WHR was positively associated with both the extent score (rs = 0.18; P < 0.05) and the myocardial score (rs = 0.17; P < 0.05) for men and women together, and positively associated with the myocardial score for women aged 40 to 70 years (rs = 0.32; P < 0.05). The associations between WHR and the CAD scores were not significant after adjusting for several risk factors for CHD. These results indicate that other risk factors for CHD may be involved in the associations between WHR and CAD.

Monthly and seasonal variation in plasma lipids in healthy Australian men: a longitudinal study in Melbourne.

A prospective study of seasonal variability of lipids in 36 healthy men, aged 40-45 years, over 14 months in Melbourne showed significant monthly and seasonal variation by paired t-test. Measurement of cholesterol and triglycerides was carried out by standard, automated enzymic assays calibrated with CDC certified materials. High Density Lipoprotein Cholesterol (HDLC) was measured after Polyethylene Glycol 6000 precipitation of Apo B containing lipoproteins. Intra-individual variation ranged wisely; Cholesterol: mean Coefficient of Variation (CV) 6.9%, range 4.1 to 14.0, HDLC: mean CV 9.1%, range 5.3 to 15.6 Low Density Lipoprotein Cholesterol (LDLC): mean CV 10.2%, range 5.2 to 18.4. The seasonal effect showed the most favourable lipid/ lipoprotein profile, ie lowest total and LDLC, highest HDLC to occur in the antipodean summer (Nov/Dec) and the least favourable profile in winter (Jul/Aug), with highest (total) Cholesterol and lowest HDLC. This is best observed as the LDLC/HDLC ratio which peaks in July (3.6), with the trough in December (2.7). This pattern is consistent with seasonal effects described previously in the northern hemisphere, except that the months are reversed. Weight did not alter significantly during the period of the study. Seasonal and individual variation in lipids and lipoproteins should be taken into account in the clinical management of lipid disorders.

Can linoleic acid contribute to coronary artery disease?

The adipose tissue concentration of linoleic acid was positively associated with the degree of coronary artery disease (CAD) in a cross-sectional study of 226 patients undergoing coronary angiography. Linoleic acid concentration in adipose tissue is known to reflect the intake of this fatty acid. These results are therefore indicative of a positive relationship between linoleic acid intake and CAD. The platelet linoleic acid concentration was also positively associated with CAD. After confounding factors were allowed for, the eicosapentaenoic acid concentration in platelets was inversely associated with CAD for men, and the docosapentaenoic acid concentration in platelets was inversely associated with CAD for women; results consistent with several other studies that suggest that fish, and omega-3 fatty acids derived from fish and fish oils, can beneficially influence macrovascular disease.

Motor effects of broad beans (Vicia faba) in Parkinson's disease: single dose studies.

Broad beans (Vicia faba) are a natural source of L-dopa. To investigate a possible role for this substance in the treatment of Parkinsonian motor oscillations, we carried out single dose studies of Vicia faba pod mixture plus carbidopa in six patients. Motor responses of equivalent magnitude to those of conventional L-dopa medication occurred in five cases with mean onset of 39 min and mean duration of 104 min. Vicia faba meals produced comparable L-dopa blood levels to fasting standard tablet doses and recovery studies yielded 0.25% L-dopa per weight of bean pod mixture. Vicia faba contains sufficient L-dopa to be pharmacologically active in patients with Parkinson's disease and can potentially be incorporated into dietary strategies to manage Parkinsonian motor oscillations.

Factors associated with successful risk reduction after a community coronary risk factor screen.

Debate continues over the effectiveness of coronary risk factor screening as a strategy for the prevention of coronary heart disease in the community. We reviewed changes in risk factors one year after a community coronary risk factor screen and found highly significant reductions in the blood cholesterol (mean reduction of 0.6 mmol/l) and body mass index (mean reduction of 1.03 kg/m2) in those participants who at the initial screening were found to have elevated (greater than 6.5 mmol/l) blood cholesterol concentrations. Comparison of this group with a reference group not given health advice and a group of hypercholesterolaemic clinic attenders showed that the blood cholesterol reduction could not be accounted for solely by regression to the mean, and was as good as the blood cholesterol reduction achieved by regular clinic attendance. Although there were many factors that could account for these reductions, we found that participants who received risk factor measurement and counselling during the screening process and who sought medical follow-up after the screen had a greater reduction in risk factors.

Risk factors for coronary heart disease in a self-referred population compared with a general population.

Screening programmes for community coronary heart disease risk factors aim to identify persons who are at a high risk of the development of coronary heart disease by screening the population for the prevalence of smoking, obesity, high blood pressure and high blood cholesterol concentrations. The effectiveness of such screening programmes is dependent on a number of factors. The characteristics of individuals who attend such screening programmes voluntarily, and the prevalence of abnormal coronary heart disease risk factors that is detected, give a strong indication of the population reach and the potential benefits of the preventive strategy. In this study, persons who attended a self-referred risk-factor screening programme for coronary heart disease were compared with a random sample of the Australian urban population. A disproportionately high number of older persons and of women presented for the self-referred screening programme while smokers were underrepresented. In general, the risk-factor levels of those in the older age-groups who attended the screening programme were lower than were the corresponding measurements that were found in the random sample; the opposite was true for those in the younger age-groups. These results suggest that coronary heart disease risk-factor screening programmes in the community appeal more to those in the health-conscious older age-groups and to women. For heart disease prevention programmes to be more effective, it will be necessary to design screening programmes to attract more men, those in younger age-groups and smokers.

Changes in plasma enzyme concentrations following intramuscular injections and gastroscopy.

The effects of intramuscular injections on plasma creatine kinase (CK), aspartate amino-transferase, lactate dehydrogenase, and hydroxybutyrate dehydrogenase concentrations were examined in 19 patients given intramuscular premedication for gastroscopy, and 18 patients given other intramuscular injections. Only CK concentrations showed significant increases which were as high as four times the upper limit of normal, and affected a maximum of 51% of patients at 12 hours after the first injection. Elevated CK concentrations persisted for up to 72 hours, and followed injections of diazepam, various antibiotics, and the combination of a narcotic analgesic with atropine. Gastroscopy did not appear to increase plasma enzyme concentrations in six patients who were given intravenous premedication. The significance of these findings to the diagnosis of myocardial infarction is discussed.