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Biomedical subjects

M Farnier

Publications and source records attributed to M Farnier.

At least 37 records · Page 2Linked to original sources
PubMed1998

Current and future treatment of hyperlipidemia: the role of statins.

Hyperlipidemia is recognized as one of the major risk factors for the development of coronary artery disease and progression of atherosclerotic lesions. Dietary therapy together with hypolipidemic drugs are central to the management of hyperlipidemia, which aims to prevent atherosclerotic plaque progression, induce regression, and so decrease the risk of acute coronary events in patients with pre-existing coronary or peripheral vascular disease. In patients at high risk of coronary artery disease but without evidence of atherosclerosis, treatment is designed to prevent the premature development of coronary artery disease, whereas in those with hypertriglyceridemia, treatment aims to prevent the development of hepatomegaly, splenomegaly, and pancreatitis. The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, or statins, are the most potent lipid-lowering agents currently available, and their use in the treatment of hyperlipidemia provides the focus for this review. Particular emphasis is given to cerivastatin, a new HMG-CoA reductase inhibitor that combines potent cholesterol-lowering properties with significant triglyceride-reducing effects. Recently completed primary and secondary intervention trials have shown that the significant reductions in low-density lipoprotein (LDL) cholesterol achieved with statins result in significant reductions in morbidity and mortality associated with coronary artery disease as well as reductions in the incidence of stroke and total mortality. Such benefits occur early in the course of statin therapy and have led to suggestions that these drugs may possess antiatherogenic effects over and above their capacity to lower atherogenic lipids and lipoproteins. Experimental studies have also shown statin-induced improvements in endothelial function, decreased platelet thrombus formation, improvements in fibrinolytic activity, and reductions in the frequency of transient myocardial ischemia.

Coronary Disease↗
PubMed1998

Cerivastatin in the treatment of mixed hyperlipidemia: the RIGHT study. The Cerivastatin Study Group. Cerivastatin Gemfibrozil Hyperlipidemia Treatment.

The Cerivastatin Gemfibrozil Hyperlipidemia Treatment (RIGHT) study--a multicenter, randomized, double-blind, placebo-controlled study--compared the lipid-lowering effects of cerivastatin, once daily at doses of 0.1, 0.2, and 0.3 mg with those of twice-daily gemfibrozil 600 mg in 751 patients with primary mixed hyperlipidemia. Randomization to the first 16 weeks of treatment followed an initial 4-week washout period and subsequent 6-week diet-controlled, placebo run-in phase. Patients continued to receive study medication for a further 36 weeks, with those previously on placebo switched to 0.1 mg/day cerivastatin at the end of week 16. Additional cholestyramine therapy was permitted at week 36 in patients with uncontrolled low-density lipoprotein (LDL) cholesterol levels. Cerivastatin achieved significant dose-dependent reductions in LDL cholesterol of 15-24% after 16 weeks of treatment, compared with reductions of 7.5% with gemfibrozil. Over this period both cerivastatin (0.3 mg) and gemfibrozil (1,200 mg) significantly decreased levels of triglycerides (20.3% vs 50.3%, respectively) and very low-density lipoprotein (VLDL) cholesterol (30.8% vs 47.1%, respectively), as well as increasing high-density lipoprotein (HDL) cholesterol (11.3% vs 13.3%, respectively). The reductions in LDL cholesterol and other atherogenic lipids and lipoproteins at 16 weeks were sustained in the subsequent 36-week double-blind continuation phase, during which time <10% of patients received additional cholestyramine therapy. Both study drugs were well tolerated, with the incidence of adverse events similar to that of placebo treatment. Clinically significant increases in hepatic transaminases and creatine phosphokinase occurred at a similar low frequency of around 1%. This study demonstrated that cerivastatin is a safe, well-tolerated, and effective treatment for lowering elevated LDL cholesterol and triglycerides in patients with mixed hyperlipidemia.

Adolescent↗
PubMed1998

Double-Blind Comparison of Apolipoprotein and Lipoprotein Particle Lowering Effects of Atorvastatin and Pravastatin Monotherapy in Patients With Primary Hypercholesterolemia.

METHODS AND RESULTS: A total of 305 subjects with primary hypercholesterolemia were randomized in a 3:1 ratio to receive either atorvastatin 10 mg daily or pravastatin 20 mg daily according to a 16-week double-blind comparative study of the effect on apolipoprotein and lipoprotein particle levels. All patients had low-density lipoprotein (LDL)-cholesterol levels between 4.2 and 6.6 mM and triglyceride concentrations below 4.5 mM at baseline. After 16 weeks of treatment, apoB (-27% and -16%; P <.001), apoE (-13.3% and -5.6%; P <.05) and the triglyceride-rich LpC-III:B particle (-33% and -26%; P <.05) levels were reduced to a significantly greater extent in the atorvastatin than in the pravastatin treatment group. Both atorvastatin and pravastatin increased apoA-I levels, an effect that was more pronounced in the pravastatin group (+7% and +11%; P <.002). The increased apoA-I levels predominated on LpA-I in the atorvastatin group (+11%) and on LpA-I:A-II in the pravastatin group (+13%). ApoA-II levels were decreased with atorvastatin to a greater extent than with pravastatin (-1% and +2.8%; P <.05). CONCLUSIONS: Although atorvastatin and pravastatin belong to the same therapeutic family, they produce different effects in apoliprotein concentrations in hypercholesterolemic patients. Atorvastatin, an agent of the new generation, appears to efficiently reduce apoB-containing lipoprotein particles containing apoC-III.

Journal Article↗
PubMed1997

Efficacy and safety of atorvastatin compared to pravastatin in patients with hypercholesterolemia.

Plasma cholesterol and other lipoproteins play a significant role in the development of atherosclerosis and subsequent coronary heart disease (CHD). This 1 year study was designed to confirm the efficacy and safety of atorvastatin (Lipitor) compared to pravastatin, a marketed agent for low density lipoprotein cholesterol (LDL-C) reduction in hypercholesterolemic patients. Patients were recruited at 26 centers in six European countries. After a 6 week placebo baseline phase, patients were randomized to receive atorvastatin 10 mg or pravastatin 20 mg daily. The dose could be doubled at week 16, if LDL-C levels remained > or = 3.4 mmol/l (135 mg/dl). Atorvastatin significantly lowered LDL-C from baseline by 35% compared with 23% for pravastatin (P < 0.05). A total of 72% of atorvastatin patients attained the LDL-C target level of < 3.4 mmol/l, compared to 26% of pravastatin patients. Atorvastatin also significantly reduced TC, TG and apo B (P < 0.05). Safety was assessed by recording adverse events and measuring clinical laboratory parameters. The adverse event profile was similar for both treatment groups and neither treatment caused clinically relevant laboratory abnormalities. Atorvastatin 10 and 20 mg once daily is superior to pravastatin 20 and 40 mg once daily in treating patients with hypercholesterolemia.

Anticholesteremic Agents↗
PubMed1995

Comparative effects of simvastatin and pravastatin on cholesterol synthesis in patients with primary hypercholesterolemia.

The effects of simvastatin and pravastatin on cholesterol biosynthesis were compared in 26 hypercholesterolemic patients who were randomly allocated to either simvastatin or pravastatin treatment (20 mg once daily) for 6 weeks in a crossover trial. Serum total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) lathosterol (latho) concentrations and lathosterol/cholesterol (latho/chol) ratios (the latter two are considered as reliable indices of whole body cholesterol synthesis) were evaluated at the beginning and end of each therapeutic sequence. Reductions in TC and LDL-C were more pronounced (P < 0.001) with simvastatin (TC = -28.0%, LDL-C = -35.6%) than with pravastatin (TC = -19.6%, LDL-C = -25.2%). These results were associated with concomitant decreases in both latho concentrations (-59.0% with simvastatin and -37.0% with pravastatin) and latho/chol ratios (-43.0% with simvastatin and -20.3% with pravastatin). Simvastatin resulted in more marked diminutions of latho concentrations (P < 0.01) and latho/chol ratios (P < 0.05) than pravastatin. These results suggest that the better efficacy of simvastatin on serum cholesterol and LDL cholesterol might result in part from a greater inhibitory action of simvastatin on cholesterol synthesis compared with that of pravastatin.

Adolescent↗
PubMed1994

Comparative efficacy and safety of micronized fenofibrate and simvastatin in patients with primary type IIa or IIb hyperlipidemia.

BACKGROUND: Few studies have been performed to compare fenofibrate, a second-generation fibrate, and simvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor. This study was aimed to compare the efficacy of both drugs in reducing atherogenic risk factors in type IIa or IIb hyperlipidemia. METHODS: Sixty-three patients entered this single-center, double-blind, crossover trial. Sixty patients (32 with type IIa and 28 with type IIb hyperlipidemia) were randomized to treatment for 3 months with a single daily 200-mg dose of micronized fenofibrate or 20 mg of simvastatin and then changed to the alternative treatment for a further 3-month period. RESULTS: After the first treatment period, in both types IIa and IIb, fenofibrate and simvastatin produced similar significant reductions in levels of total cholesterol and low-density lipoprotein cholesterol; high-density lipoprotein cholesterol levels were increased with both drugs in type IIb. Only fenofibrate decreased total triglyceride levels in type IIb, Lp(a) lipoprotein levels in patients with high baseline values, and fibrinogen. After the second period of treatment, in both types IIa and IIb, switching from fenofibrate to simvastatin resulted in a further reduction in total cholesterol and low-density lipoprotein cholesterol levels. The difference in the response of the two treatments on levels of total triglycerides, Lp(a) lipoprotein, and fibrinogen was confirmed after changing over to the alternative treatment. This short-term study showed few adverse effects for both drugs. CONCLUSIONS: Fenofibrate and simvastatin provide similar variations on total cholesterol and low-density lipoprotein cholesterol levels after a 3-month treatment period, with simvastatin having the capacity to decrease these measures further when administered after fenofibrate. However, fenofibrate exhibits a significant effect on other established risk factors, such as total triglyceride, fibrinogen, and Lp(a) lipoprotein levels, and accordingly has a broader spectrum of activity than simvastatin.

Adolescent↗
PubMed1993

Variations in the fatty acid composition of lipid classes from lipoproteins in elderly women.

Fatty acid composition of lipid classes and NMR spectra of lipoproteins were compared in 6 young (24-35-year-old) and 6 elderly (79-90-year-old) women. Cholesteryl ester, triglyceride and protein content of LDL in elderly women were significantly higher (+52-57% and +20% for lipids and proteins, respectively) than those observed in young women. HDL lipid levels were similar in the two groups. The proportion of linoleic acid (mainly in cholesteryl esters and phospholipids) of each lipoprotein species was always lower in octogenarians when compared with young females (lowering of 13-28% and 27-46% for cholesteryl esters and phospholipids, respectively). Conversely, the proportions of mono-unsaturated fatty acids (mainly oleic acid) increased in all lipid classes, although this was only significant in cholesteryl esters from each lipoprotein species. NMR spectra of lipoproteins showed a restricted mobility of acyl chain terminal CH3 groups in old women which was significant only in VLDL and HDL3. This suggests that the decrease of linoleic acid could affect the lipid mobility in lipoproteins of elderly women.

Adult↗
PubMed1992

[The "duration of administration" factor in studies of clinical pharmacology of hypolipemic drugs].

Clinical pharmacological trials of lipid lowering drugs should first of all indicate the duration of interruption of previously used lipid lowering drugs. The duration of interruption should be at least 4 weeks for inhibitors of HMG CoA reductase, 6 weeks for a second generation fibrate or a resin and over 6 months for probucol. In order to obtain the maximum therapeutic effect, a 4 week treatment period is sufficient for a HMG CoA reductase inhibitor or a resin. On the other hand, this period is longer for a fibrate and a 6 week treatment period is to be preferred with this family of drugs. The efficacy of probucol on the lipid fractions can only be assessed after several months' therapy. In future, a more accurate classification of patients with respect to their physiopathology should provide a better evaluation of the comparative efficacy of the different lipid lowering drugs.

Clinical Trials as Topic↗
PubMed1990

Human low density lipoprotein subfractions separated by gradient gel electrophoresis: composition, distribution, and alterations induced by cholesteryl ester transfer protein.

Low density lipoprotein (LDL) subfractions were studied in sera from 208 normolipidemic, 22 hypercholesterolemic, and 33 hypertriglyceridemic subjects. Whole serum without preliminary ultracentrifugation was submitted to electrophoresis in a nondenaturing polyacrylamide gel. Three main LDL patterns were observed in normolipidemic sera: type 1, characterized by the presence of only one major band; type 2, characterized by the presence of two close major bands; and type 3, where LDL were more dispersed and presented at least three distinct bands. Type 1 was more frequent in men (43%) than in women (19%). The tendency for a higher potential coronary disease risk profile sera, namely higher triglyceride level, higher very low density lipoprotein + LDL fraction and lower high density lipoprotein (HDL) fraction, was type 3 less than type 2 less than type 1. The LDL patterns found in hypercholesterolemic sera were of type 1. Hypertriglyceridemic sera were characterized by the presence of a major band of small size. Separated LDL subfractions were collected by electroelution and analyzed for composition. In all subspecies, the mass ratio of core to surface components was constant as well as the molar ratio of the two lipid surface components, phospholipids and free cholesterol. Surface lipid to apolipoprotein B ratio, cholesteryl ester to triglyceride ratio, and cholesteryl ester to apoB ratio increased with particle size increment. Incubation of LDL with HDL and purified cholesteryl ester transfer protein induced a transfer of lipids, mainly cholesteryl esters and phospholipids, to LDL and an increase of the sizes of LDL subfractions. This suggests that lipid transfers from HDL to LDL might be a process of intravascular LDL remodeling and a factor of LDL polymorphism.

Adolescent↗
PubMed1989

[Prostatic tumors. Detection by proton nuclear magnetic resonance spectroscopy of plasma lipoproteins].

Recently, there has been interest over detection of malignant tumors by water-Suppressed Proton Nuclear Magnetic Resonance Spectroscopy (1 HNMR) of plasma lipoproteins (N. Engl. J. Med., 1986, 315, 1369-76). We performed a similar prospective and blinded study comprising 75 subjects; 40 control (C), 15 untreated prostate cancer patients (PC) and 20 patients with benign prostate tumors (BT). We measured the parameter W 1/2, as mean of the full width at half height of the resonances of the methyl and methylene groups of the lipids of the plasma lipoproteins which is inversely related to the spin-spin apparent relaxation time (T2*). W 1/2 values were determined at a fixed baseline of 310 Hz. The W 1/2 mean values were 37.6 +/- 3.7 Hz for C, 37.4 006 5.2Hz for PC and 36.4 +/- 3.9 Hz for BT, essentially identical for all three groups. Furthermore, no difference was seen between any group on scatter pattern that could serve as a basis for a useful detection test. The major difficulty in the determination of W 1/2 was due to interference of metabolite protons (lactate) within the lipoprotein resonance signal. There was no correlation seen between W 1/2 triglyceride, total cholesterol, HDL-cholesterol and (LDL + VLDL)-cholesterol levels. We conclude the Water-Suppressed 1HNMR Spectroscopy of plasma lipoproteins as performed, is not a valid method for detection of prostate cancer.

Adenocarcinoma↗
PubMed1988

Direct quantitation of serum high density lipoprotein subfractions separated by gradient gel electrophoresis.

This report describes the densitometric quantitation of the two main HDL subfractions separated by electrophoresis in a polyacrylamide gradient gel, HDLS (mean apparent diameter 9.3 nm) and HDLL (mean apparent diameter 10.6 nm). The electrophoresis was carried out in a linear gradient of polyacrylamide ranging from 23 to 180 g/l on total sera prestained for lipid components by Sudan black B in ethylene glycol. HDL subfractions were quantified by scanning the gels at 633 nm with a laser densitometer. The precision was checked by intra-assay and between-assay studies (coefficient of variation 1.2 and 2.9%, respectively). The results were compared with the cholesterol content of HDL subfractions (r = 0.99) and with the HDL2:HDL3 distribution (r = 0.95). Reference values were obtained from a population of 214 normolipidemic subjects. They were in good agreement with those already published for HDL2 and HDL3. The method which needs only 4 microliter of serum, can be set up with currently available apparatus and is compatible with large series of samples, should allow large scale explorations of the variation of HDL subfraction distribution in normal and pathological populations.

Adult↗
PubMed1988

Proton nuclear magnetic resonance spectroscopy of plasma lipoproteins in malignancy.

A recent study (N. Eng. J. Med. 315 (1986), 1369), described a method of detecting malignant tumors by water-suppressed proton nuclear magnetic resonance (1 H NMR) study of plasma. We performed a similar study of the W 1/2, a mean of the full width at half height of the resonances of the methyl and methylene groups of the lipids of plasma lipoproteins which is inversely related to the spin-spin apparent relaxation time (T 2*). W 1/2 values were measured at a fixed baseline width of 310 Hz. The study was prospective and blinded and comprised 182 subjects consisting of 40 controls, 68 patients with untreated malignancies, 45 with malignant tumors undergoing therapy and 29 benign tumor patients. No differences were seen between any groups that could serve as a basis for a useful clinical test. The major difficulty in the determination of W 1/2 was due to interference of metabolite protons (particularly lactate) within the lipoprotein resonance signal. Triglyceride level was seen to correlate inversely with W 1/2 within malignant patient groups. These discrepant results may be related to differing triglyceride-rich very low density lipoprotein (VLDL) levels in the patient populations of each study. We conclude that the water-suppressed 1H NMR of plasma lipoproteins is not a valid measurement for assessing malignancy.

Female↗
PubMed1988

[Influence of acute hyperinsulinism on arterial pressure of diabetics. Reproducibility of the hypotensive effect].

We have observed effects of acute hyperinsulinaemia on arterial pressure of five diabetics and tested the reproducibility of this action. Systolic (TAS) and diastolic (TAD) arterial pressure were studied during two hyperinsulinaemic-euglycaemic clamps effected with Artificial Pancreas (Biostator CGIIS, Miles) at one month of interval. During the first clamp, between the beginning of insulin infusion and the end of 4th stage, we have observed a fall of TAS (115 +/- 4, VS 137 +/- 6 mmHg; moy +/- SEM; p less than 0.05) and in less degree of TAD (76 +/- 2, VS 86 +/- 4 mmHg; NS). These modifications of arterial pressure were associated with no changes of heart rate and urinary sodium flow. On the other hand, we have observed a fall of serum levels of sodium (139 +/- 1, VS 141 +/- 1 mEq/l; p less than 0.05), urea (0.20 +/- 0.01, VS 0.32 +/- 0.02 g/l; p less than 0.001) whereas, balance-sheet of water was positive (+445 +/- 338 ml) at the end of clamp. During the second clamp, the fall of pressure has been reproducible, relating to the TAS (123 +/- 5, VS 145 +/- 4 mmHg; p less than 0.01) and non significantly to the TAD (78 +/- 2, VS 88 +/- 5 mmHg; NS). During the two tests, the mean of tension fall was identical (22 +/- 6 mmHg during first clamp, 22 +/- 4 mmHg during second one). So, acute hyperinsulinaemia induces a fall of arterial pressure, probably in bringing an influence on arterial vasodilatation since heart rate and urinary sodium excretion are unchanged and water balance-sheet is positive.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗
PubMed1987

[Reference values of serum transferrin in newborn infants, children and adults].

The authors have studied the evolution of serum transferrin concentration in relation with age (newborn child, infant, adult). The mean concentration of serum transferrin is the lowest for neonates (2.15 g/l). At 10 months, it increases to reach a value of about 3.10 g/l then reduces at 24 (3.0 g/l) and 48 months (2.8 g/l). By the 4 to 18 years subjects, serum transferrin is approaching that of 10 months children (3.15 g/l). At last it doesn't support any modification during all the adult life. The diversity of the obtained results dependent of the used technique and/or of the laboratory, justifies that each one defines his own reference values.

Adolescent↗