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Biomedical subjects

J L Richard

Publications and source records attributed to J L Richard.

At least 73 records · Page 4Linked to original sources
PubMed1992

Upper-body fat distribution: a hyperinsulinemia-independent predictor of coronary heart disease mortality. The Paris Prospective Study.

The Paris Prospective Study is a long-term investigation of the factors predicting coronary heart disease in a large population of middle-aged men. The first follow-up examination involved 7,152 subjects, who were natives of metropolitan France and were free of any cardiovascular history. At that time, the usual cardiovascular risk factors and plasma insulin levels were recorded. An index of body fat distribution, the iliac-to-thigh ratio, was entered into the list of predictive variables, despite the fact that it had been measured 1 year before the first follow-up examination. After 11 years of mean follow-up, 129 of the men had died of coronary heart disease. Univariate analysis showed that the iliac-to-thigh ratio (p < 0.0001) and plasma insulin level (both fasting [p < 0.003] and 2-hour postload [p < 0.02]), as well as the four major risk factors of coronary heart disease (age, smoking, blood pressure, and plasma cholesterol level) were significantly higher in subjects who died of coronary heart disease compared with those who had died of another cause or were alive at the end of follow-up. In multivariate stepwise logistic regression, the iliac-to-thigh ratio appeared as an independent predictor of coronary heart disease death, thereby causing the removal of fasting insulin level from the list of significant independent predictors. Nevertheless, in a model that entered 2-hour postload insulin in two classes (high or low), both the insulin level and iliac-to-thigh ratio were found as significant independent predictors.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1992

[Trials of primary prevention by diet or hypolipidemic treatment].

The experimental demonstration of a causal relationship between serum cholesterol and coronary artery disease has been confirmed by primary prevention trials. Four trials have fulfilled the methodological criteria of this type of research. Three of them have involved lipid lowering drugs (clofibrate, cholestyramine and gemfibrozil) and the fourth a diet low in saturated fats. They were undertaken in middle aged hypercholesterolemic men and offered 9 out of 10 chances of demonstrating a significant reduction in the prevalence in ischaemic heart disease if it existed. The serum cholesterol of the treatment groups was on average 8 to 13% lower to that of the control groups. In the 4 trials, the prevalence of severe coronary events, infarction and sudden death, was significantly reduced (relative reduction of 19 to 47%). The reduction in individual risk was proportional to the reduction in serum cholesterol. In 2 trials, this reduction was related to variations in the opposite directions of the LDL and HDL cholesterol: a reduction of 1% in LDL-cholesterol reduced the risk by 2% and an increase of 1% of HDL-cholesterol reduced it by 2 to 4%. None of the trials were designed to evaluate the effect of intervention on mortality. In one of them (clofibrate), all cases of mortality were temporarily increased during the trial.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

[Blood cholesterol and mortality].

Mortality rates vary with serum cholesterol levels: the causal nature of this relationship is studied by prospective studies (analysis of associations) and unifactorial primary prevention trials (experimentation to determine causality). In prospective studies all cause mortality is often increased at low and high cholesterol levels because of the inverse relationships of this factor with cardiovascular mortality (positive) and non-cardiovascular mortality (negative). Coronary death increases proportionally to serum cholesterol levels in all populations, including those with low cholesterol levels, in both sexes and at all ages. The relationship with cerebrovascular mortality seems to depend on the clinical feature: increased mortality rate due to cerebral haemorrhage in patients with low serum cholesterol and a positive correlation with cerebral thrombosis. Mortality due to cancers is generally negatively correlated to serum cholesterol levels with a significant increase in mortality in patients with a low serum cholesterol. This relationship often becomes less significant as the time between measurement and death increases. Mortality due to violent causes is not usually related to serum cholesterol. The multitude of possible causes of confusion makes any causal interpretation of data illusory. Experimentation by unifactorial primary prevention trials is essential for any etiological research but none of the trials performed to date was designed to analyse the effect of lowering serum cholesterol on global or coronary mortality.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

[Relations between HDL-cholesterol and cardiovascular diseases].

Many retrospective and prospective epidemiological studies have demonstrated an inverse relationship between HDL-cholesterol and coronary risk. The predictive value of HDL-cholesterol is observed both in asymptomatic subjects and those with a primary vascular event. Several genetic abnormalities may be responsible for low HDL cholesterol (under 100 mg/dl or 0.26 mmol/l) or for a less severe hypoalphalipoproteinaemia. Despite some very low values, these rare causes of HDL deficiency are not all atherogenic and serve to emphasize the complexity of HDL metabolism. The protective role of HDL is explained by a number of mechanisms such as their role in the reverse transport from the peripheral tissues to the liver, their anti-oxidant effect and the increase in prostacyclin levels. The correction of isolated hypoalphalipoproteinaemia by drugs is controversial, but associated hyperlipidaemic states would be an indication to use drugs which increase the HDl-cholesterol the most.

Apolipoprotein A-I↗
PubMed1992

[Role of triglycerides in cardiovascular diseases].

The role of triglycerides in cardiovascular disease is a controversial subject. Despite differences of opinion, present data allow a certain number of conclusions to be drawn. Hyperchylomicronemia is not associated with atherosclerosis, whereas type III hyperlipidemia is very atherogenic. These two abnormalities are, however, rare, and the majority of hypertriglyceridemias are, in practice, associated with increased very low density lipoproteins. Many epidemiological trials do not identify hypertriglyceridemia as an independent risk factor when the cholesterol and, in particular, the HDL cholesterol levels, are taken into consideration. Nevertheless, these results must be interpreted with caution as hypertriglyceridemia represents a very heterogeneous entity which is closely related to many factors which affect coronary risk (hypertension, insulin resistance, sedentarity, and even tobacco consumption). Therefore, hypertriglyceridemia and hypo-HDL-emia may be the result of the same primary abnormality; as the HDL-cholesterol level is more stable, it is the parameter which will be identified as a protective factor in epidemiological trials. The available data is insufficient to affirm that therapeutic lowering of triglycerides is accompanied by a reduced coronary risk because none of the large scale trials were designed to analyse this problem. Despite these epidemiological data, the measurement of serum triglyceride levels remains important in patients with hyperlipidemia.

Cholesterol, HDL↗
PubMed1992

[Serum cholesterol and cancer. Is there a causal relationship?].

Several studies have reported an inverse relationship between serum cholesterol levels and the risk of cancer, especially of the colon (Seven Countries, Framingham, Chicago studies, London Whitehall Study, Paris prospective study, New Zealand Maori, Honolulu Heart Study, Hypertension Detection and Follow-Up Program, ...). For example, in the Multiple Risk Factor Intervention Trial (361 662 men), the global mortality graph was J-shaped, higher at either side of the 4.6-5.1 mmol/l value of serum cholesterol. This increased mortality with lower serum cholesterol levels was due to increased numbers of death from cancer. However, when the relationship is studied with respect to the time elapsed between the cholesterol measurement and death from cancer, the relative risk of death in the lowest decile with respect to the average of the following deciles, decreases with the period between measurement of the serum cholesterol and time of death. The negative relationship between serum cholesterol and death by cancer, very significant for deaths occurring within the first 5 years, disappeared almost completely for deaths occurring after 5 years. Other trials designed mainly to examine cardiovascular risk, and concerning smaller numbers, have not demonstrated this inverse relationship between serum cholesterol and cancer. This negative relationship between serum cholesterol and cancer must be acknowledged. It is weak and concerns mainly colonic cancer, especially in men in the elderly age groups. Several explanations have been put forward: influence of the combination of factors, competition of risk of death by other causes, chance, alteration of normal biological function of the cell membrane.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

[Is regression of atherosclerosis possible?].

Experimental studies have shown the regression of atherosclerosis in animals given a cholesterol-rich diet and then given a normal diet or hypolipidemic therapy. Despite favourable results of clinical trials of primary prevention modifying the lipid profile, the concept of atherosclerosis regression in man remains very controversial. The methodological approach is difficult: this is based on angiographic data and requires strict standardisation of angiographic views and reliable quantitative techniques of analysis which are available with image processing. Several methodologically acceptable clinical coronary studies have shown not only stabilisation but also regression of atherosclerotic lesions with reductions of about 25% in total cholesterol levels and of about 40% in LDL cholesterol levels. These reductions were obtained either by drugs as in CLAS (Cholesterol Lowering Atherosclerosis Study), FATS (Familial Atherosclerosis Treatment Study) and SCOR (Specialized Center of Research Intervention Trial), by profound modifications in dietary habits as in the Lifestyle Heart Trial, or by surgery (ileo-caecal bypass) as in POSCH (Program On the Surgical Control of the Hyperlipidemias). On the other hand, trials with non-lipid lowering drugs such as the calcium antagonists (INTACT, MHIS) have not shown significant regression of existing atherosclerotic lesions but only a decrease on the number of new lesions. The clinical benefits of these regression studies are difficult to demonstrate given the limited period of observation, relatively small population numbers and the fact that in some cases the subjects were asymptomatic. The decrease in the number of cardiovascular events therefore seems relatively modest and concerns essentially subjects who were symptomatic initially. The clinical repercussion of studies of prevention involving a single lipid factor is probably partially due to the reduction in progression and anatomical regression of the atherosclerotic plaque.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

[Optimal serum cholesterol and efficacy of methods for lowering cholesterolemia].

Analysis of epidemiological studies enables definition of the optimal serum cholesterol level between 2 and 2.2 g/l (5.2 and 5.7 mmol/l). Higher levels are associated with an exponential risk of coronary artery disease: lower levels should be interpreted with caution because of the J-shaped curve of global mortality reported in several trials. In primary prevention, therapeutic trials have clearly shown that a significant reduction in the number of coronary event may be obtained by lowering the serum cholesterol (15 for every 1,000 patients treated). In trials performed to date this benefit has not resulted in any gain in global mortality. In secondary prevention, the benefits of lowering serum cholesterol on the incidence of coronary disease seems identical in terms of relative risk to that observed in primary prevention. Nevertheless, the benefits in terms of absolute risk are much higher because of the high incidence of coronary mortality in a patient population with a previous coronary event. Thus, for 1,000 patients treated, there are 50 less cardiac events and this is reflected in a reduction of global mortality of about 20 for every 1,000 patients treated.

Cholesterol↗
PubMed1992

[Should men aged 20 to 30 years with hypercholesterolemia be managed in the same way as older men?].

Serum cholesterol intervention studies have been mainly performed in middle-aged men. Is the extrapolation of these results to men aged 20 to 30 years justified? Atherosclerosis is a process which continues throughout life. It is clear that increased serum cholesterol levels are associated with a higher coronary risk. In addition, serum cholesterol levels increase with age up to 60 years old. Do young men obtain the same benefits from medical intervention as older men? Therapeutic trials have been performed in middle-aged men. The increase in life expectancy associated with a 6.7% lowering of the serum cholesterol by life-long dietary restrictions would only be 4 months in 20 year old subjects at high risk (hypertension, smokers, low HDL cholesterol). With a 20% reduction in serum cholesterol, the gain would be 12 months. There is no reason for not extrapolating acquired data in the over 30s to 20 to 30 year old subjects. Due to the fact that young subjects are exposed to the risk for longer periods, it is advisable to treat their hypercholesterolaemia even more seriously than that of older patients.

Adult↗
PubMed1992

[Should hypercholesterolemic women be treated?].

There have been few studies designed to evaluate the problem of hypercholesterolaemia in women despite the fact that, like men, cardiovascular disease is their main cause of death. Serum cholesterol is a risk factor in women, but the increased risk appears at much higher values of serum cholesterol than observed in men. In women, low HDL-cholesterol seems to be the best predictive factor for the occurrence of a coronary event, especially if the triglycerides are raised. The absence of therapeutic data on the treatment of hypercholesterolaemia in women underlines the need for a specific trial to assess the effects of lipid-lowering drugs in this population. The cardiovascular benefits of hormone substitute therapy at the menopause have been reported in several studies and a large scale randomised trial is under way to confirm these results. The benefit of hypercholesterolaemic therapy in women with mild hypercholesterolaemia has not been proved. When the serum cholesterol level is over 3 g/l (7.77 mmol/l), early treatment is advisable.

Adult↗
PubMed1992

[Hyperlipidemia in patients over 60 years old].

The management of hyperlipidemia in individuals aged 60 or over is a serious problem, given the frequency of metabolic abnormalities in this age group. The decision to treat must take into account a number of uncertainties. Hypercholesterolemia is a risk factor in the elderly and, in general, its importance varies like the other major risk factors (hypertension and smoking): the relative risk decreases with age but this decrease in relative risk is associated with an increase in the absolute risk because the prevalence of cardiovascular disease greatly increases with age. The serum cholesterol level increases with age but the physiopathological mechanism os this increase is poorly understood (reduction in the number of LDC receptors?). In the over 70s, serum cholesterol levels decrease, probably because of a selection due to the deaths of subjects at higher risk. No therapeutic trials have been performed to evaluate the effects of lowering the serum cholesterol in the over 60s. In addition, strict application of international recommendations in this age group would result in a large number of therapeutic interventions, the value of which would be questionable. Under these conditions, practical clinical advice is based on reasoned extrapolation of epidemiological data obtained in middle-aged men. Treatment should therefore be reserved for sever forms of hyperlipidemia, taking into consideration the life expectancy of the individual.

Aged↗
PubMed1992

[Comparison of prognosis and treatment of myocardial infarction in Haute-Garonne between 1986 and 1989. MONICA project, Toulouse].

The aim of this study, based on the data of the MONICA register in the Haute-Garonne, was to compare the prognosis and treatment of myocardial infarction between 1986 (253 cases) and 1989 (248 cases). The clinical features of these infarcts were comparable except for the previous history of ischaemic heart disease which was less common in 1989 (34.7% in 1986, 25.9% in 1989; p < 0.05). The 28th day mortality decreased from 8.4% in 1986 to 3.6% in 1989 without attaining statistical significance. The pre-hospital management was the same during the two periods of the study, with 67.6% of patients admitted to hospital before the 6th hour. Hospital care in 1986 and 1989 consisted of 5 days in the intensive care unit and lasted 14 days. Treatment changed considerably from 1986 to 1989. There was a higher incidence of platelet antiaggregant prescriptions (47.4% in 1986 and 80% in 1989; p < 0.001), of betablocker prescriptions (30.8% in 1986 and 47% in 1989; p < 0.05) and fibrinolytics (27.8% in 1986 and 52% in 1989; p < 0.01). Invasive procedures such as coronary angiography (83.5% in 1986 and 94% in 1989; p < 0.05), coronary angioplasty (20.3% in 1986 and 53.5% in 1989; p < 0.01) were undertaken in the majority of cases. The MONICA-Toulouse project shows a reduction in mortality and an increase in the use of therapeutic methods known to be effective in the reduction of mortality in myocardial infarction.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Hyperinsulinaemia as a predictor of coronary heart disease mortality in a healthy population: the Paris Prospective Study, 15-year follow-up.

The Paris Prospective Study is a long-term, large-scale study of the factors predicting coronary heart disease. The first follow-up examination included, for subjects not known as having diabetes mellitus, a 75 g oral glucose tolerance test with measurement of plasma insulin and glucose levels, fasting and 2 h post-load. Between 1968 and 1973, 6903 men aged 43-54 years were thus examined. Causes of death were ascertained within this group after 15 years of mean follow-up. The baseline variables were tested as predictors of death from coronary heart disease by a Cox regression analysis. Significant independent predictors of coronary heart disease death were: systolic blood pressure, number of cigarettes per day, plasma cholesterol level, and 2 h post-load plasma insulin level when entered as a categorical variable (below or above 452 pmol/l. i.e. the lower limit of the fifth quintile of the distribution). This dichotomization was performed to account for the non-linear univariate distribution of deaths with increasing post-load insulin values. Fasting plasma insulin level was not an independent predictor of death by coronary heart disease over this long-term follow-up. Levels of blood glucose were not significant independent predictors of death by coronary heart disease when plasma insulin levels were included in the model. The same applied to abnormalities of glucose tolerance when the 125 men with known non-insulin-treated diabetes at baseline were added to the group. Under the assumption that hyperinsulinaemia is a marker of insulin resistance, the results are consistent with the hypothesis that insulin resistance is associated with a higher risk of coronary heart disease mortality. However, it is doubtful that circulating insulin per se is a direct cause of arterial complications.

Biomarkers↗
PubMed1991

Concentrations of fumonisin B1 in feeds associated with animal health problems.

Ninety-eight samples of feeds associated with 44 cases of equine leukoencephalomalacia (ELEM) and 83 samples of feed associated with 42 cases of a porcine pulmonary edema syndrome (PPE) were analyzed for fumonisin B1 (FB1). For comparison purposes, 51 feed samples not associated with PPE or ELEM were also analyzed. Feed associated with ELEM contained FB1 ranging from less than 1 microgram/g to 126 micrograms/g with 75% of the cases having at least 1 sample above 10 micrograms/g. Feeds associated with PPE ranged from less than 1 microgram/g to 330 micrograms/g with 71% of the cases having at least 1 sample greater than 10 micrograms/g. Quantitation was by high performance liquid chromatography (HPLC)/fluorescence using the fluorescamine derivative with confirmation by thin layer chromatography (TLC) and/or gas chromatography/mass spectroscopy (GC/MS).

Animal Feed↗
PubMed1991

Secretogranin I (chromogranin B) mRNA accumulation is hormonally regulated in GH3B6 rat pituitary tumor cells.

Secretogranin I (SgI; chromogranin B) belongs to a class of acidic tyrosine-sulfated secretory proteins believed to play a role in the secretory process of endocrine cells. Our aim here was to compare the levels of SgI mRNA to that of prolactin (PRL) and growth hormone (GH), using rat pituitary cell lines. As far as the constitutive expression is concerned, we found a positive correlation between SgI mRNA and PRL mRNA levels. However, the neuropeptide TRH (50 nM) inhibited the accumulation of SgI mRNA in GH3B6 cells whereas, as expected, it induced a rapid and sustained increase in PRL mRNA accumulation. By contrast, 17 beta-estradiol (1 nM) stimulated the accumulation of both SgI and PRL mRNAs, with the same EC50 (18-59 pM). Reciprocally, treatment with dexamethasone (100 nM) reduced the level of SgI and PRL mRNAs to 23% and 29% of control, respectively, but led to a 2.1-fold increase in the GH mRNA level. Altogether, the present work shows that SgI gene expression is subject to multiple hormonal regulations and occasionally parallels the regulation of the PRL gene but never that of the GH gene, under the conditions tested.

Animals↗
PubMed1991

The high risk of death by alcohol related diseases in subjects diagnosed as diabetic and impaired glucose tolerant: the Paris Prospective Study after 15 years of follow-up.

The 15 year mortality rates and causes of death are reported for the Paris Prospective Study cohort of 7180 working men, aged between 44 and 55 years who attended the first follow-up examination. All subjects were classified as normoglycaemic, impaired glucose tolerant or diabetic according to the WHO criteria, following an oral glucose tolerance test. The relative risks of death in comparison to the normoglycaemic group were 1.6 for impaired glucose tolerant and 2.3 for diabetic subjects; for death due to coronary heart disease: 1.7 and 2.3 respectively; for death due to alcohol and cirrhosis: 7.0 and 13.3 respectively. It appears that in this cohort a proportion of subjects screened as diabetic have impaired liver function and disturbed carbohydrate metabolism, due to excessive alcohol consumption. Alcohol should be investigated as a possible risk factor for diabetes, particularly in epidemiological studies where diabetes is diagnosed by the oral glucose tolerance test and the population has a high consumption of alcohol.

Adult↗