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Biomedical subjects

C Sanllehy

Publications and source records attributed to C Sanllehy.

14 recordsLinked to original sources

Randomized crossover study of gemfibrozil versus lovastatin in familial combined hyperlipidemia: additive effects of combination treatment on lipid regulation.

The most appropriate therapy for combined hyperlipidemia remains to be determined. We compared the lipid-regulating effects of gemfibrozil and lovastatin in 30 patients with familial combined hyperlipidemia (FCHL) in a randomized, double-blind, placebo-controlled crossover study including 8-week courses of one drug followed by a washout period and a crossover phase to the alternate drug. After completion of the trial, open-label combination therapy was given for up to 12 months. Lovastatin was more efficacious than gemfibrozil in the reduction of total cholesterol (23% v. 9%, P<.001) and low-density lipoprotein (LDL) cholesterol (28% v. 2%, P<.001), whereas gemfibrozil surpassed lovastatin in the reduction of triglycerides (48% v. 0%, P<.001) and very-low-density lipoprotein (VLDL) cholesterol (50% v. 19%, P = .005) and the increase of high-density lipoprotein (HDL) cholesterol (18% v. 4%, P = .005). Lovastatin caused a greater decline in total apolipoprotein B (apo B) and LDL apo B than gemfibrozil, whereas VLDL apo B decreased only after gemfibrozil therapy. Drug-induced changes in lipoprotein composition indicated that gemfibrozil reduced both the number and size of VLDL particles and lovastatin decreased the number of LDL particles. Combined treatment was safe and had additive effects on lipids, causing significant (P<.001) reductions in total cholesterol (32%), triglycerides (51%), LDL cholesterol (34%), and apo B (26%) and an increase in HDL cholesterol (19%). Target LDL cholesterol levels were achieved only in 11% of patients given gemfibrozil alone and triglycerides decreased to target levels in 22% after lovastatin alone, whereas combined therapy normalized both lipid fractions in 96% of patients. Thus, in FCHL, gemfibrozil has no effect on LDL cholesterol levels but favorably influences the putative atherogenic alterations of lipoprotein composition that are related to hypertriglyceridemia. Conversely, lovastatin markedly decreases LDL cholesterol but has little effect on triglyceride-rich lipoproteins. Combination treatment safely corrects all of the lipid abnormalities in most patients.

Adult↗

Lack of interaction of apolipoprotein E phenotype with the lipoprotein response to lovastatin or gemfibrozil in patients with primary hypercholesterolemia.

The magnitude of serum lipid changes in response to hypolipidemic drugs varies considerably between individuals. These differences may be due to interactions between genetic and environmental factors that effect drug bioavailability or the capacity of the lipid-regulating enzyme and receptor targets to be affected. The apolipoprotein E (apoE) gene locus has been examined in this regard, but reports are conflicting on the effect of its variability on the response to hypolipidemic drugs. We investigated the effect of apoE polymorphism on the serum lipid response to the hepatic hydroxymethyl glutaryl coenzyme A (HMG CoA) reductase inhibitor lovastatin and the fibric acid derivative gemfibrozil. Lipoprotein changes were assessed after 12 weeks of therapy in 106 patients with primary hypercholesterolemia and combined hyperlipidemia treated with lovastastin and in 63 given gemfibrozil therapy. No significant effect of the apoE phenotypes E3/2, E3/3, or E4/3 on the heterogeneity of lipid responses to either drug was found.

Adult↗

Normal and gestational diabetic pregnancies. Lipids, lipoproteins and apolipoproteins.

OBJECTIVE: To evaluate plasma lipids, lipoproteins and apolipoprotein changes induced by gestational diabetes. STUDY DESIGN: In this case-control study, 60 women between 26 and 32 weeks of pregnancy were allocated to four groups according to lipid status and glucose tolerance: (1) normolipemia and no gestational diabetes, (2) normolipemia and gestational diabetes, (3) hyperlipemia and no gestational diabetes, and (4) hyperlipemia and gestational diabetes. Total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, very low density lipoprotein cholesterol (VLDLc), triglycerides, triglycerides/very low density lipoprotein (VLDL), apolipoproteins (APO) A1 and APO B, APO B-VLDL and APO B/low-density lipoprotein were measured. RESULTS: There were no statistically significant differences in the normolipemic group of women. Among the hyperlipemic patients, gestational diabetic women showed lower VLDLc when compared to nondiabetic patients. CONCLUSION: Our results, comparing groups separated groups by lipid status, show that the only difference in lipid profile associated with glucose intolerance is lower VLDLc in hyperlipemic patients.

Apolipoproteins↗

First-trimester biochemical screening for Down syndrome with the use of PAPP-A, AFP, and beta-hCG.

Biochemical screening for Down syndrome (DS) is well established in the second trimester of pregnancy, but there is little information available on its value in the first trimester. This study describes our preliminary results with biochemical screening for DS in the first trimester of pregnancy in order to evaluate its efficacy at this time. Our study population, including 19 DS pregnancies, was evaluated using maternal serum levels of alpha-fetoprotein (AFP), beta-human chorionic gonadotropin (beta-hCG), and pregnancy-associated plasma protein A (PAPP-A). At a false positive rate (FPR) of 5 per cent, the detection rate (DR) for DS is 9 per cent for beta-hCG, 18 per cent for AFP, and 66 per cent for PAPP-A when considering these parameters individually. With different combinations of the analytes, the best detection rates are obtained with the association of PAPP-A and AFP (85 and 82 per cent DR for a 10 and 5 per cent FPR, respectively). Our data support the value of first-trimester biochemical screening for DS and that of PAPP-A as a single marker.

Adult↗

Apolipoprotein E polymorphism and gallstones.

BACKGROUND & AIMS: Apolipoprotein (apo) E is a genetically polymorphic protein influencing lipoprotein metabolism and the risk of both atherosclerosis and Alzheimer's disease. As opposed to common apo E3, apo E2 decreases and apo E4 increases hepatic lipoprotein uptake; hence, apo E4 could promote gallstone formation by increasing hepatic and biliary cholesterol concentrations. This study was designed to evaluate whether apo E polymorphism is related to gallstone risk. METHODS: apo E phenotype was determined in subjects older than 40 years of age (160 with and 125 without gallstones) and in 61 patients with cholesterol gallstones who underwent cholecystectomy. Bile composition, nucleation time, and gallstone features were analyzed in surgical patients. RESULTS: The E4/3 phenotype was enriched in both patients with gallstones and those who underwent cholecystectomy, with significantly (P < 0.006) higher epsilon 4 allele frequencies than in gallstone-free subjects (odds ratio, 2.67 [95% confidence limits, 1.23-5.93] and 3.62 [95% confidence limits, 1.49-8.91], respectively); women, but not men, accounted for these differences. The prevalence of the epsilon 4 allele increased with age in patients with gallstones, whereas the opposite occurred in gallstone-free subjects. Biliary lipid and gallstone cholesterol content tended to increase in the sequence E4 > E3 > E2 in patients who underwent cholecystectomy. CONCLUSIONS: Carrying the apo E4 isoform is a genetic risk factor for cholelithiasis in humans, thus adding another adverse effect of apo E polymorphism on health.

Adult↗

Plasma lipids, lipoproteins and apolipoproteins in hirsute women.

OBJECTIVE: To determine whether lipid alterations in hirsute women are due to excessive androgen, low estrogen or to a combination of these abnormalities. DESIGN: Cross sectional study. PATIENTS: Forty-five hirsute women between 15 and 39 years of age. MAIN OUTCOME MEASURES: FSH, LH, 17beta-estradiol, PRL, testosterone, androstenedione, triglycerides and apolipoproteins A-I and B. RESULTS: Testosterone was correlated with triglycerides (r: 0.76, p<0.01), HDL (r: -0.61, P<0.01) and LDL (r: 0.50, p<0.05). Both HDL (r: 0.66, p<0.01) and LDL (r: -0.57, p<0.01) were correlated with estradiol. Total cholesterol was also correlated with estradiol (r: -0.52, p<0.05). Cross adjusted correlations revealed that, after adjusting for estradiol, lipids were associated with testosterone and that estradiol was also correlated with lipids when adjusted for testosterone. CONCLUSION: The results suggest that altered lipids in women with hyperandrogenism could result from independent effects of androgens and estrogens.

Adolescent↗

Variation in lipid levels during pregnancy in women with different types of hypertension.

OBJECTIVES: To evaluate the levels of serum lipids (cholesterol and triglycerides) in pregnant women with different types of hypertension, at the first, second and third trimesters of pregnancy. METHODS: Cholesterol and triglyceride levels at the first, second and third trimesters of gestation were recorded for 115 women with hypertension during pregnancy, and 115 healthy pregnant women matched for age and body mass index. Cases were classified as having mild gestational hypertension (25), severe gestational hypertension (15), mild preeclampsia (20), severe preeclampsia (20), chronic hypertension (20), and superimposed preeclampsia (15). RESULTS: Cholesterol levels were not statistically different between cases and controls in any form of hypertension. At 20 and 34 weeks' gestation, triglyceride levels were significantly higher than controls in women with severe gestational hypertension, mild and severe preeclampsia, and superimposed preeclampsia, but not in mild gestational hypertension or chronic hypertension. The significant elevation in triglycerides was already present at 10 weeks in mild and severe preeclampsia. CONCLUSIONS: The data suggest that the alterations in lipid metabolism observed in preeclampsia are already present at the first trimester of pregnancy. Women with severe gestational hypertension presented a pattern of triglycerides similar to that of preeclamptic women, but mild gestational hypertension resembled chronic hypertension in this respect. This supports the concept that, although in many cases gestational hypertension represents latent essential hypertension, some of these women, probably the most severe cases, present with true pregnancy-induced hypertension, or nonproteinuric preeclampsia.

Adult↗

Effects of progestogen on lipids, lipoproteins and apolipoproteins during transdermal estrogen replacement therapy with and without medroxyprogesterone acetate.

OBJECTIVE: To assess whether the effects on plasma lipids and lipoproteins after oophorectomy differ in patients who receive transdermal estrogen replacement therapy (ERT) with and without progestin. STUDY DESIGN: Twenty-five healthy, normal-weight, regularly menstruating women who underwent hysterectomy and bilateral oophorectomy for benign diseases received, for one year, transdermal therapeutic systems containing estradiol with daily delivery of 50 micrograms cyclically for 24 days per month plus 2.5 mg/d of oral medroxyprogesterone acetate (MPA) sequentially for the last 12 days of each cycle. After the first year the patients ceased to take MPA. We determined the levels of cholesterol (CHOL), high density lipoprotein (HDL)-CHOL, low density lipoprotein (LDL)-CHOL, triglycerides (TG) and apolipoproteins (apo) A-I and B prior to oophorectomy, one month after surgery and during the 6th and 12th months on estrogen plus progestogen substitution and during the 18th and 24th months without progestogen addition. RESULTS: After oophorectomy, the patients showed increases in LDL, apo-B and atherogenic index, whereas after hormone replacement therapy the patients exhibited falls in plasma LDL, apo-B and atherogenic index and increases in HDL and apo A-I. No significant changes in total CHOL were observed after surgery or treatment, and TG were decreased. Plasma levels of lipids and lipoproteins during estrogen replacement therapy (ERT) without MPA were not significantly different from those observed during ERT plus MPA. CONCLUSION: Changes in lipids induced by transdermal ERT were not affected by low doses of MPA.

Administration, Cutaneous↗

[Carotid atherosclerosis evaluated by two-dimensional ultrasonography in patients with primary hypercholesterolemia].

BACKGROUND: Two-dimension ultrasonography permits to noninvasively quantify extracoronary atherosclerosis. The objective of this study was to assess preclinical atherosclerosis of the extracranial carotid arteries in patients with primary hypercholesterolemia. METHODS: Lipid and nonlipid cardiovascular risk factors were evaluated in 206 patients with dyslipidemia (127 men and 79 women, mean age 49 years, range 18-75), and a multifactorial cardiovascular risk profile was constructed for each patient. Ultrasound measurements of the intima-media thickness in the common carotid artery of each side were taken, and the number and height of any atheroma plaques present were quantified. RESULTS: Asymptomatic plaques were found in 120 patients (58%), and were more frequent in men than in women (65 vs 47%, p = 0.009), and in patients with than in those without prior coronary heart disease (80 vs 50%, p < 0.001). Both intimal thickening, indicative of early atherosclerosis, and the extent of arterial wall involvement with plaques, which represents an advanced stage of the disease, increased significantly with age and with increasing multifactorial cardiovascular risk, reflecting a positive relation between signs of atherosclerosis and the burden of risk factors. Intima-media thickness also increased with increasing plaque score, indicating the generalization of atherosclerosis. CONCLUSIONS: The high prevalence of preclinical carotid atherosclerosis confirms the atherogenic risk of primary dyslipidemias. The relation between carotid lesions and both coronary heart disease and multifactorial risk supports the validity of arterial ultrasound studies for cardiovascular risk prediction.

Adolescent↗

Effect of apolipoprotein E polymorphism on the serum lipid response to a hypolipidemic diet rich in monounsaturated fatty acids in patients with hypercholesterolemia and combined hyperlipidemia.

We investigated the effect of variation at the apolipoprotein (apo) E gene locus on the serum lipid response to a hypolipidemic diet rich in monounsaturated fatty acids (MUFA). Lipoprotein changes were assessed in 122 outpatients with type IIa (n = 70) and type IIb (n = 52) hyperlipidemia [80 men and 42 women with apo E phenotypes 3/2 (n = 27), 3/3 (n = 48), and 4/3 (n = 47)] who were switched from their basal diet containing 40% fat (22% MUFA) to an isoenergetic diet containing 31% fat (MUFA content similar to that of the basal diet) for 12 wk. Significant (P < 0.005) reductions of total, LDL, and VLDL cholesterol; triglycerides; and apo B occurred in subjects regardless of WHO phenotype. Triglycerides and VLDL cholesterol decreased more in type IIb than in type IIa subjects: 25% vs 12% and 21% vs 15%, respectively (P = 0.01). HDL cholesterol tended to decrease only in women. The heterogeneity of lipoprotein responses to dietary intervention was unrelated to apo E phenotypes. In these hyperlipidemic subjects, however, diet-induced favorable changes in serum lipoproteins were selectively influenced by WHO phenotype.

Adult↗

Postmenopausal hormone replacement therapy with low-dose medroxyprogesterone acetate. Endometrium, plasma lipids, lipoproteins and apolipoproteins.

Several studies have demonstrated that the use of estrogens in postmenopausal women has a protective effect against cardiovascular disease; however, this beneficial effect may be counteracted when concomitant progestogens are administered. We investigated the influence of hormone replacement therapy (HRT) with lower doses of medroxyprogesterone acetate (MPA) (2.5 mg/d) on the endometrium and on the plasma levels of lipids, lipoproteins and apolipoproteins. All the studied HRT regimens induced favorable changes in the levels of plasma lipids, lipoproteins and apolipoproteins, which may play an important role in the prevention of cardiovascular disease. The dosage of 2.5 mg/d of MPA is clearly inadequate to protect the endometrium from hyperplastic changes with sequential regimens, but probably this dosage is safe when MPA is administered continuously.

Adult↗

Effects of oophorectomy and hormone replacement therapy on plasma lipids.

The aim of this study was to determine the effects on plasma lipids and lipoproteins of oophorectomy and various hormone replacement therapy (HRT) delivery systems using low doses of medroxyprogesterone acetate (MPA, 2.5 mg/day). A total of 90 women completed the 1-year follow-up period. Patients were randomly assigned to five groups. The first (n = 16) received 0.625 mg/day conjugated equine oestrogens (CEE) cyclically, the second (n = 20) 50 micrograms/day transdermal oestradiol cyclically and the third (n = 15) 0.625 mg/day CEE continuously. These three groups also received 2.5 mg MPA sequentially for the last 12 days of HRT administration. The fourth group (n = 20) received 0.625 mg/day CEE and 2.5 mg/day MPA continuously, while the fifth (n = 19) constituted a treatment-free control group. After oophorectomy patients showed increases in low-density lipoprotein (LDL), apolipoprotein B and the atherogenic index, whereas after HRT patients exhibited falls in plasma LDL, apolipoprotein B and the atherogenic index and increases in high-density lipoprotein (HDL) and apolipoprotein A1. No significant changes in total cholesterol were observed after surgery or treatment and decreased levels of triglycerides were detected only in the transdermal treatment group.

Apolipoproteins↗

Comparative study of a microporous cholestyramine analogue (filicol) and gemfibrozil for treatment of severe primary hypercholesterolemia. Short- and long-term results.

The hypolipidemic effect of gemfibrozil in severe hypercholesterolemia is not well established. Fifty patients with primary hypercholesterolemia (including 18 patients with familial hypercholesterolemia) and stable low-density lipoprotein cholesterol levels greater than 3.90 mmol/L (greater than 150 mg/dL) (6.10 +/- 1.30 [SD] mmol/L; 236 +/- 50 mg/dL) while on a hypolipidemic diet were assigned to treatment for 12 weeks with either 9 g/d of filicol, a microporous cholestyramine analogue, or 1.2 g/d of gemfibrozil in a randomized clinical trial. Tolerance was good with both drugs. Filicol and gemfibrozil caused similar decrements of total cholesterol (14% for both), low-density lipoprotein cholesterol (20% and 18%, respectively), and apolipoprotein B (16% and 21%, respectively). Close to 40% of the patients had decreases of greater than 25% in low-density lipoprotein cholesterol levels with both drugs. Gemfibrozil, but not filicol, significantly increased plasma high-density lipoprotein cholesterol (16%) and apolipoprotein A-I (17%) levels and reduced triglyceride levels (35%). No loss of efficacy was observed with either drug in subsets of patients who had a good 12-week response rate and had extended therapy for up to 12 months. This study demonstrates that gemfibrozil may have a beneficial effect on all aspects of the plasma lipid profile in patients with severe hypercholesterolemia, a clinical situation where it can be used with potential advantages over standard doses of anion-exchange resins.

Adult↗

A new immunonephelometric method for amniotic fluid alpha-fetoprotein measurement.

We have evaluated the analytic performance of a new immunonephelometric method developed for the measurement of amniotic fluid alpha-fetoprotein (AF-AFP) and compared it with the classic immunoradiometric method used up to now. Intrassay precision, evaluated for three AF-AFP levels, was good and Interassay imprecision shows higher coefficients of variation (CVs) especially for medium and high AF-AFP levels. Linearity was demonstrated for level higher than 300,000 ng/ml and no hook effects was observed. Comparison with an IRMA method gave the following regression equation: y = 3050 + 0.52X (r = 0.76, p less than 0.001, n = 36).

Amniotic Fluid↗