Altered signal pathway in granulocytes from patients with hypercholesterolemia.
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In the present study the signal transduction of the formyl-Met-Leu-Phe receptor was studied in granulocytes obtained from control subjects and patients with elevated low density lipoprotein levels. According to our results, 10 nm formyl-Met-Leu-Phe in control cells activates phospholipase C inducing a pronounced inositol phosphate production followed by a Ca(2+) signal from intracellular pools. The pertussis toxin-sensitive O(2)(-) generation and leukotriene synthesis were moderate. In contrast, in granulocytes from hypercholesterolemic patients, formyl-Met-Leu-Phe triggered an intensive pertussis toxin-insensitive oxidative burst and leukotriene synthesis. The inositol trisphosphate and Ca(2+) signals were decreased significantly in granulocytes of hypercholesterolemic patients and seem to be dependent on the extracellular Ca(2+) content. Furthermore, in the resting granulocytes of hypercholesterolemic patients the [Ca(2+)]i and the membrane-bound protein kinase C activity were higher than in controls, the time of normalization after the low Ca(2+) signal was delayed, while the membrane fluidity was decreased. Our results suggest that in these ex vivo experiments, the high level of circulating low density lipoprotein in patients can affect the membrane composition of granulocytes leading to altered signal transduction by the formyl-Met-Leu-Phe receptor, to altered Ca(2+) pump-activity, and protein kinase C translocation. (+info)
An independent association between obstructive sleep apnoea and coronary artery disease.
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Previous studies of sleep and breathing suggest an independent association between coronary artery disease (CAD) and obstructive sleep apnoea (OSA) in middle-aged males and females. These studies, however, were criticized because they did not properly adjust for all important confounding factors. In order to better control for the impact of these confounders, a case-control study was performed, matching for age, sex and body mass index (BMI), and additionally adjusting for hypertension, hypercholesterolemia, diabetes mellitus and current smoking. A consecutive selection of 62 patients (44 males and 18 females, mean age 69 yrs, range 44-88 yrs) requiring intensive care for angina pectoris or myocardial infarction at the County Hospital of Skaraborg, Skovde, Sweden, as well as 62 age-, sex- and BMI- matched control subjects without history or signs of heart disease underwent an overnight sleep/ventilatory monitoring study. The time interval between discharge from the intensive care unit and the overnight study ranged between 4 and 21 months. OSA, defined as a Respiratory Disturbance Index (RDI) of > or =10 x h(-1), was present in 19 CAD patients but only in eight control subjects (p=0.017). Using a univariate logistic regression analysis, current smoking (odds ratio (OR) 8.1, 95% confidence interval (CI) 2.2-29.0), diabetes mellitus (OR 4.2, 95% CI 1.1-16.1) and OSA (OR 3.0, 95% CI 1.2-7.5), but not hypertension (OR 1.5, 95% CI 0.7-3.2) and hypercholesterolaemia (OR 1.8, 95% CI 0.7-4.1) were significantly correlated with CAD. In a multiple logistic regression model, current smoking (OR 9.8, 95% CI 2.6-36.5), diabetes mellitus (OR 4.2, 95% CI 1.1-17.1) and OSA (OR 3.1, 95% CI 1.2-8.3) all remained independently associated with CAD. In summary, these data suggest a high occurrence of obstructive sleep apnoea in middle-aged and elderly patients with coronary artery disease requiring intensive care, which should be taken into account when considering risk factors for coronary artery disease. (+info)
Cardiovascular health check in the elderly in one general practice: does it offer new information and lead to interventions?
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BACKGROUND: Prevention of cardiovascular disease in the elderly is becoming increasingly important. GPs are in a unique position to initiate preventive interventions in this age group. However, it is not clear which strategy a GP should follow to identify patients at increased cardiovascular risk-case finding or screening. OBJECTIVE: We aimed to assess the value of a single cardiovascular health check compared with a normal care case finding and to investigate the diagnostic or therapeutic consequences of detecting new cardiovascular risk indicators. METHODS: In 1991, 1002 persons aged 60 years and over, enlisted in one general practice, were invited. Of the 805 subjects who responded (80%), the cardiovascular risk profile was determined by a research physician. The proportion of newly detected cardiovascular risk indicators was the main outcome measure. A risk indicator was considered newly detected when it was not mentioned in the GP's summary of the patient record, which had been checked by the patient for its completeness. The patient records of participants with newly detected hypertension, diabetes or hypercholesterolaemia were systematically reviewed to detect diagnostic and therapeutic interventions by the GP. RESULTS: In 25.1% of the participants, one or more cardiovascular risk indicators were found which were previously unknown to the GP, including 38 (4.7%) cases of hypertension, 82 (10%) cases of isolated systolic hypertension, 14 (1.7%) cases of diabetes mellitus and 63 (7.8%) cases of hypercholesterolaemia. On the basis of these findings, the GP initiated therapeutic interventions in almost all subjects with newly detected diabetes. However, reports of newly detected hypertension or high cholesterol levels were usually not followed by an intervention. CONCLUSION: A single cardiovascular health check in the elderly can detect a considerable number of risk indicators that are unknown to a patient's GP. In most cases, however, the detection of hypertension or cholesterol > or = 6.5 mmol/l did not lead to interventions by the GP. More efforts are needed to ensure that the beneficial effects of these interventions are not limited to participants in clinical trials but can be extended to patients in general practice. (+info)
Addition of arginine but not glycine to lysine plus methionine-enriched diets modulates serum cholesterol and liver phospholipids in rabbits.
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Previous experiments from our laboratory showed that in rabbits fed an amino acid diet corresponding to 30% casein, enrichment of the diet with L-lysine and L-methionine caused a marked increase in serum total and LDL cholesterol levels as well as a substantial body weight loss. Both effects were partially prevented by supplementation with L-arginine. The present studies were designed to extend this earlier observation by assessing the role of different dietary amino acids in modulation of cholesterolemic responses and body weights. In the first experiment, the original lysine and methionine-enriched diet was supplemented with glycine in an attempt to modify methionine metabolism, and thus to reduce body weight loss. In addition, the mechanism of action of lysine and methionine was investigated by quantitation of major liver phospholipids. The results showed that glycine addition had no effect on weight loss or hypercholesterolemia, nor did it alter plasma levels of homocyst(e)ine, an intermediate in methionine metabolism. However, enrichment of the diet with lysine and methionine (with or without glycine) significantly increased liver levels of phosphatidylcholine and the ratio of phosphatidylcholine to phosphatidylethanolamine, apparently through increased enzymatic conversion. These changes were consistent with higher lipoprotein levels and thus may explain the hypercholesterolemia. A second experiment showed that similar effects on body weights and serum cholesterol could be obtained by adding lysine and methionine to a diet containing amino acids equivalent to only 15% casein, or 15% intact casein. This approach is more physiologic and also reduces the expense of experiments designed to study the effects of lysine and methionine in more detail. (+info)
Dietary defatted sesame flour decreases susceptibility to oxidative stress in hypercholesterolemic rabbits.
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Plant glucosides possess antioxidative properties due to their ability to scavenge free radicals. Sesame seeds contain a class of these compounds, the sesaminol glucosides. To evaluate their antioxidative activity in vivo, we fed rabbits diets containing 1% cholesterol (Chol) with or without 10% defatted sesame flour (DSF) (containing 1% sesaminol glucosides) for 90 d. We determined the susceptibility of their tissues to oxidation ex vivo as well as serum total cholesterol (TC), phospholipid (PL), triglyceride (TG) and HDL cholesterol (HDL-C) concentrations. Serum TC, HDL-C, PL and TG levels were unaffected by the addition of DSF. The HDL-C in the Chol + DSF group was greater than in the Chol group at 45 d. Both were greater than in the groups that did not consume cholesterol. Liver TC and TG were significantly lower in rabbits fed the diet containing DSF plus 1% cholesterol than in those fed 1% cholesterol alone. Lipid peroxidation activity, measured as 2-thiobarbituric acid reactive substances (TBARS), was lower in the liver (P < 0.05) and serum (P = 0.06) of rabbits fed DSF plus cholesterol than in rabbits fed the cholesterol diet. Although we did not detect sesaminol glucosides in peripheral tissues, we observed abundant quantities of sesaminol in rabbits fed DSF, the principal metabolite. Our findings suggest that feeding DSF to rabbits does not protect cholesterol-induced hypercholesterolemia, but may decrease susceptibility to oxidative stress in rabbits fed cholesterol, perhaps due to the antioxidative activity of sesaminol. (+info)
Effects of psyllium on glucose and serum lipid responses in men with type 2 diabetes and hypercholesterolemia.
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BACKGROUND: Water-soluble dietary fibers decrease postprandial glucose concentrations and decrease serum cholesterol concentrations. This study examined the effects of administering psyllium to men with type 2 diabetes. OBJECTIVE: The objective was to evaluate the safety and effectiveness of psyllium husk fiber used adjunctively to a traditional diet for diabetes in the treatment of men with type 2 diabetes and mild-to-moderate hypercholesterolemia. DESIGN: After a 2-wk dietary stabilization phase, 34 men with type 2 diabetes and mild-to-moderate hypercholesterolemia were randomly assigned to receive 5.1 g psyllium or cellulose placebo twice daily for 8 wk. Serum lipid and glycemic indexes were evaluated biweekly on an outpatient basis and at weeks 0 and 8 in a metabolic ward. RESULTS: In the metabolic ward, the psyllium group showed significant improvements in glucose and lipid values compared with the placebo group. Serum total and LDL-cholesterol concentrations were 8.9% (P < 0.05) and 13.0% (P = 0.07) lower, respectively, in the psyllium than in the placebo group. All-day and postlunch postprandial glucose concentrations were 11.0% (P < 0.05) and 19.2% (P < 0.01) lower in the psyllium than in the placebo group. Both products were well tolerated, with no serious adverse events related to treatment reported in either group. CONCLUSION: The addition of psyllium to a traditional diet for persons with diabetes is safe, is well tolerated, and improves glycemic and lipid control in men with type 2 diabetes and hypercholesterolemia. (+info)
Lifetime health and economic benefits of weight loss among obese persons.
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OBJECTIVES: This study estimated the lifetime health and economic benefits of sustained modest weight loss among obese persons. METHODS: We developed a dynamic model of the relationship between body mass index (BMI) and the risks and costs of 5 obesity-related diseases: hypertension, hypercholesterolemia, type 2 diabetes, coronary heart disease (CHD), and stroke. We then calculated the lifetime health and economic benefits of a sustained 10% reduction in body weight for men and women aged 35 to 64 years with mild, moderate, and severe obesity. RESULTS: Depending on age, gender, and initial BMI, a sustained 10% weight loss would (1) reduce the expected number of years of life with hypertension, hypercholesterolemia, and type 2 diabetes by 1.2 to 2.9, 0.3 to 0.8, and 0.5 to 1.7, respectively; (2) reduce the expected lifetime incidence of CHD and stroke by 12 to 38 cases per 1000 and 1 to 13 cases per 1000, respectively; (3) increase life expectancy by 2 to 7 months; and (4) reduce expected lifetime medical care costs of these 5 diseases by $2200 to $5300. CONCLUSIONS: Sustained modest weight loss among obese persons would yield substantial health and economic benefits. (+info)
Behavioural counselling in general practice for the promotion of healthy behaviour among adults at increased risk of coronary heart disease: randomised trial.
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OBJECTIVE: To measure the effect of behaviourally oriented counselling in general practice on healthy behaviour and biological risk factors in patients at increased risk of coronary heart disease. DESIGN: Cluster randomised controlled trial. PARTICIPANTS: 883 men and women selected for the presence of one or more modifiable risk factors: regular cigarette smoking, high serum cholesterol concentration (6.5-9.0 mmol/l), and high body mass index (25-35) combined with low physical activity. INTERVENTION: Brief behavioural counselling, on the basis of the stage of change model, carried out by practice nurses to reduce smoking and dietary fat intake and to increase regular physical activity. MAIN OUTCOME MEASURES: Questionnaire measures of diet, exercise, and smoking habits, and blood pressure, serum total cholesterol concentration, weight, body mass index, and smoking cessation (with biochemical validation) at 4 and 12 months. RESULTS: Favourable differences were recorded in the intervention group for dietary fat intake, regular exercise, and cigarettes smoked per day at 4 and 12 months. Systolic blood pressure was reduced to a greater extent in the intervention group at 4 but not at 12 months. No differences were found between groups in changes in total serum cholesterol concentration, weight, body mass index, diastolic pressure, or smoking cessation. CONCLUSIONS: Brief behavioural counselling by practice nurses led to improvements in healthy behaviour. More extended counselling to help patients sustain and build on behaviour changes may be required before differences in biological risk factors emerge. (+info)