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R Carmena

Publications and source records attributed to R Carmena.

At least 37 records · Page 2Linked to original sources
PubMed2001

Association between the TaqIB polymorphism in the cholesteryl ester transfer protein gene locus and plasma lipoprotein levels in familial hypercholesterolemia.

Cholesteryl ester transfer protein (CETP) facilitates the exchange of triglycerides (TG) and cholesteryl ester between lipoprotein particles. Subjects with familial hypercholesterolemia (FH) have been reported to have higher CETP activities, which could contribute to the lower high-density lipoprotein-cholesterol (HDL-C) levels and increased cardiovascular risk observed in some of these patients. Several polymorphisms have been reported in the CETP locus; the common TaqlB polymorphism is associated, in normolipidemic subjects, with decreased CETP activity and levels and with increased HDL-C levels. No data is available on the influence of this polymorphism in FH subjects. We have examined the TaqIB polymorphism in a group of 101 FH heterozygotes from Valencia, Spain. We have observed a frequency of 0.43 for the B2 allele, similar to those reported in the general population. Based on analysis of variance (ANOVA), we found significant associations between the presence of the B2 allele and increased plasma HDL-C (P <.04) and apolipoprotein A-I (apoA-I) levels (P <.01). An opposite association was observed for low-density lipoprotein-cholesterol (LDL-C) levels, with the B2/B2 subjects having lower levels than B1/B1 and B1/B2 subjects. The plasma apoB levels followed the same trend as those for LDL-C. In addition, the response to a National Cholesterol Education Program (NCEP)-I diet was studied in 77 of these subjects. The TaqlB polymorphism did not have a significant effect over the individual dietary response for any of the variables examined, as demonstrated by the lack of significant gene by diet interactions. In summary, the CETP TaqlB polymorphism is associated with a less atherogenic lipid profile, consisting of lower LDL-C, higher HDL-C levels, and a lower LDL-C/HDL-C ratio in heterozygous FH subjects. Moreover, the B2 allele was associated with a lower appearance of arcus cornealis, xanthomata, and clinical arteriosclerotic disease in these subjects.

Adult↗
PubMed2001

Genetic diagnosis of familial hypercholesterolemia in a South European outbreed population: influence of low-density lipoprotein (LDL) receptor gene mutations on treatment response to simvastatin in total, LDL, and high-density lipoprotein cholesterol.

The aims of this study were to examine the presence of mutations in the low-density lipoprotein receptor gene among subjects clinically diagnosed with familial hypercholesterolemia and to analyze whether the molecular diagnosis helps to predict the response to simvastatin treatment in our familial hypercholesterolemia population. Fifty-five probands and 128 related subjects with familial hypercholesterolemia were studied. Genetic diagnosis was carried out following a three-step protocol based on Southern blot and PCR-single strand conformational polymorphism analysis. A randomized clinical trial with simvastatin was conducted in 42 genetically diagnosed subjects with familial hypercholesterolemia classified as carriers of null mutations (n = 22) and of defective mutations (n = 20). A mutation-causing familial hypercholesterolemia was identified in 46 probands (84%). In 41 of them (89%), a total of 28 point mutations were detected, 13 of which have not been previously described. The remaining five probands (11%) were carriers of large rearrangements. Familial hypercholesterolemia with null mutations showed a poor response to simvastatin treatment. The mean percentage reduction of plasma total and low-density lipoprotein cholesterol levels in these subjects were significantly lower (24.8 +/- 10.3 vs. 34.8 +/- 10.9, P = 0.04 and 30.0 +/- 39.8 vs. 46.1 +/- 18.2, P = 0.02, respectively) than in subjects with defective mutations. Baseline and posttreatment high-density lipoprotein cholesterol plasma values were significantly lower in subjects with familial hypercholesterolemia with null mutations (P < 0.001). In an outbreed Caucasian population, a three-step protocol for genetic screening detected a mutation in the low-density lipoprotein receptor gene in a high percentage (84%) of subjects with familial hypercholesterolemia. Subjects with familial hypercholesterolemia with null mutations (class I) showed lower plasma high-density lipoprotein cholesterol values and a poor low-density lipoprotein cholesterol response to simvastatin treatment.

Adult↗
PubMed2001

Impact of obesity in primary hyperlipidemias.

Obesity is frequently associated with high plasma triglyceride and reduced plasma high-density lipoprotein (HDL)-cholesterol (HDL-C) levels, and an increased concentration of apoB-carrying lipoproteins. The effects of obesity on lipid metabolism are mainly mediated by insulin resistance and, as central (visceral) obesity significantly increases insulin resistance, it aggravates these lipid changes. We have reviewed the impact of obesity on lipid metabolism in different types of primary hyperlipidemias. Obesity is not common in primary (familial and polygenic) hypercholesterolemias, and insulin resistance is infrequent; various investigators have found no or only a weak association between plasma cholesterol concentrations and insulin levels. On the other hand, in familial hypertriglyceridemia (type IV) and familial combined hyperlipidemia (FCH), obesity and insulin resistance are common and, when present, contribute to a further deterioration in the lipid profile. Weight loss in most of these patients is accompanied by a significant decrease in plasma triglyceride levels and an increase in HDL-C. Reviewing the data published by our group, we show that insulin resistance is an important component of the metabolic derangement in FCH subjects; high fasting plasma free fatty acids and triglycerides levels correlate to insulin resistance, thus linking this abnormality to lipid metabolism. A high waist/hip ratio (indicating visceral fat deposits) exacerbates insulin resistance, but this is also present in lean FCH subjects. Furthermore, insulin resistance is associated with a higher prevalence of coronary heart disease in this group of subjects.

Adipose Tissue↗
PubMed2000

Coexisting dysbetalipoproteinemia and familial hypercholesterolemia. Clinical and laboratory observations.

Type III dysbetalipoproteinemia and familial hypercholesterolemia (FH) are two metabolic disorders giving rise to severe disturbances of lipid homeostasis and premature atherosclerosis. Both metabolic abnormalities have a genetic basis and co-occurrence in the same patient has seldom been described. Because of the unique structure of the French Canadian population, there was an opportunity to observe patients with both dysbetalipoproteinemia (E2/2 homozygotes) and FH (N=14) and to compare their clinical data with that of patients with type III (N=75), patients with FH (N0.7 and the presence of beta-VLDL on electrophoresis. Presence of a low density lipoprotein receptor, LDL-R, mutation should be suspected in a type III patient with a LDL-C level above 3.0 mmol/l and a family history of premature CAD. In the group of patients studied, the coexistence of dysbetalipoproteinemia and heterozygous FH does not appear to increase the prevalence of cardiovascular complications above that observed among control type III or control E3/3-FH patients. Thus, the presence of two epsilon2 alleles in these patients affects the expression of the abnormal LDL-R allele and the resulting phenotype substantiates the non additive effects of alleles at these two loci (epistasis).

Adult↗
PubMed2000

Lipoprotein phenotype and insulin resistance in familial combined hyperlipidemia.

The study objective was to investigate the relationship of insulin resistance (IR) with the lipoprotein phenotype in familial combined hyperlipidemia (FCH). Thirty-seven FCH men diagnosed by clinical and biochemical criteria and classified as lipoprotein phenotype IIa (n = 9), IIb (n = 17), or IV (n = 11) were compared with a healthy control group of 30 men of similar age, body mass index (BMI), waist to hip ratio (WHR), and systolic and diastolic blood pressure. In all subjects, the plasma lipoprotein profile and baseline and post-oral glucose tolerance test (OGTT) glucose and insulin plasma values were measured. An intravenous glucose tolerance test was performed and IR was studied by the peripheral insulin sensitivity index (Si). After the OGTT, significantly higher values for insulinemia (at 0, 60, 90, and 120 minutes) and the area under the curve (AUC) of insulin secretion were observed in FCH. The AUC of insulin was greater in FCH subjects with the hypertriglyceridemic phenotype as compared with the controls and significantly lower Si levels, indicating greater IR, were found in the three FCH groups (control, 3.48 +/- 1.87 mU/L/min; FCH IIa, 2.09 +/- 1.08; FCH IIb, 1.54 +/- 0.77; FCH IV, 1.47 +/- 0.93; P < .001). The prevalence of IR (Si < 2 x 10(-4) mU/L/min) was greater in FCH, independent of the lipoprotein phenotype, as compared with the controls (P < .0001). Higher plasma glucose and insulin levels at 120 minutes and lower Si values were found in the FCH IIa group compared with the controls (P < .05), indicating a state of IR in this subgroup of normotriglyceridemic subjects. In conclusion, IR was found in the three FCH lipoprotein phenotypes, being more severe in subjects with hypertriglyceridemia. Hence, the therapeutic goals in FCH should include measures to normalize plasma lipids and improve peripheral insulin sensitivity.

Adult↗
PubMed2000

Comparative study of two techniques for assessing fat intake in a Mediterranean diet. The influence of culinary oils changes.

The diet usually consumed by a community of 18 normolipemic monks was studied. It included olive oil as cooking fat (basal period BP). This diet was modified by substituting olive oil for sunflower oil during a 21-day period (experimental period EP). The precise individual weighing technique was utilised for the determination of intake, and by means of the food composition tables (FCTs) the energy and nutrient of the diet were calculated. By chemical analysis of the duplicate sample (CA) of the cooked dishes the lipid intake was also determined. Total serum cholesterol HDL and LDL cholesterol, serum triglycerides, AI and B-100 apolipoproteins and Lp(a) were also analysed. Similarly the absolute and relative values for SFA, MUFA and PUFA obtained by both techniques were also different and these were maintained when the (PUFA + MUFA)/SFA ratio was calculated by both techniques and in the two periods. The correction of the lipid intake by means of the CA technique did not improve either the correlation between the intake or the plasma lipid concentration or the cholesterolemia prediction (r = 0.83 for FCT and CA).

Adult↗
PubMed2000

Ciprofibrate effects on carbohydrate and lipid metabolism in type 2 diabetes mellitus subjects.

BACKGROUND AND AIMS: Atherosclerosis is the most common cause of morbidity and mortality in type 2 diabetes mellitus. Hyperglycemia, dyslipoproteinemia, arterial hypertension and coagulation abnormalities are the most important cardiovascular risk factors. Hypertriglyceridemia and low high density lipoprotein-cholesterol (HDLc) seem to be related with insulin resistance. Fibric acid derivates (fibrates) are effective in the treatment of dyslipoproteinemia in diabetes. Our aim was to evaluate the efficacy and safety of ciprofibrate in improving dyslipoproteinemia and its effect on fibrinogen plasma concentrations, carbohydrate metabolism variations and insulin action. METHODS AND RESULTS: 13 subjects with type 2 diabetes mellitus were treated with diet and placebo for 4 weeks and then randomized to one of two treatments: ciprofibrate 100 mg or placebo for four weeks. After a four-week wash-out period they were crossed over as shown in Figure 1. Total cholesterol, triglycerides, low density lipoprotein-cholesterol (LDLc), very low density lipoprotein-cholesterol (VLDLc), HDLc, Apolipoprotein B100, fibrinogen, insulin and Lp(a) were measured. Insulin erythrocytes union was made by the Gambhir method. There was a 15% decrease in total cholesterol (p < 0.05) and 47% decrease in triglycerides (p < 0.01); similar changes were observed in VLDL-cholesterol and VLDL-triglycerides; 17% increase in HDL-cholesterol (p < 0.05). No significant differences were observed in LDL-cholesterol, apolipoprotein B100 and lipoprotein (a). Fibrinogen decreased 10% (p < 0.05). A non-significant 10% decrease in insulin secretion (area under curve) after oral glucose was observed with ciprofibrate. These findings indicate a decrease in receptor affinity. A non-significant decrease in insulin receptor number/cells was also observed. CONCLUSIONS: Ciprofibrate has a potent hypolipidemic effect, especially a decrease in triglycerides, VLDL and fibrinogen, and an increase in HDL-cholesterol, but does not influence glycemic control nor insulin action. Decreased insulin secretion may be due to peripheral use of glucose due to the drug's antilipolytic action.

Adult↗
PubMed2000

Effect of apolipoprotein E genotype on lipid levels and response to diet in familial hypercholesterolemia.

The response of plasma lipids to dietary fat and cholesterol is partly genetically controlled. Apolipoprotein (Apo) E polymorphism has been shown to influence basal plasma lipid levels and the response to dietary changes in normolipidemic individuals. In general, subjects carrying the E4 allele have higher basal total and low density lipoprotein cholesterol (LDL-C) plasma levels and show an increased LDL-C response to dietary manipulation. The response to diet in subjects with familial hypercholesterolemia (FH) is also variable, but the influence of apo E genotypes on their dietary response has received little attention. We studied such influence on the lipid response to the National Cholesterol Education Program type I (NCEP-I) diet in 69 FH heterozygotes (44 women and 25 men). Subjects were studied at baseline (after consuming for 1 month a diet with 35% fat [10% saturated] and 300 mg cholesterol) and after 3 months of consuming a low-fat diet. No sex-related differences were found, and results were combined for men and women. The frequency distribution of apo E alleles was similar to that described in the general Spanish population: 0.0724 for the E2 allele, 0.0724 for E4 and 0.8551 for E3. Baseline plasma lipid and lipoprotein values were not influenced by apo E genotype. The response to the NCEP-I diet was similar in all subjects and no apoE allele-related differences were identified. As in non-FH subjects, there was a nonsignificant trend towards greater LDL-C lowering in E4 (-19.3%) than in E3 (-18.2%), and E2 (-16.6%) carriers. This finding supports the hypothesis that the impact of genetic defects at the low density lipoprotein receptor (LDLR) locus in FH subjects prevails over any influence on the part of ApoE polymorphism.

Adult↗
PubMed1999

[Familial defect of apo B-100 in subjects with clinically diagnosed primary hypercholesterolemia: identification of the first family with this disorder in Spain].

BACKGROUND: The aim of our study was to screen mutations responsible of FDB in subjects with primary hypercholesterolemia. MATERIAL AND METHODS: We have screened R3500Q and other mutations (PCR-SSCP analysis) in 110 subjects with primary hypercholesterolemia from the Valencia area (Spain), 95 of them with familial hypercholesterolemia (FH) and 15 with poligenic hypercholesterolemia (PHC). RESULTS: One out of 95 subjects carried the R3500Q mutation. We have searched in the family and have identified another affected subject. CONCLUSIONS: We have identified the first affected Spanish family from FDB. The prevalence of R3500Q mutations was of 1% in FH subjects in this series.

Apolipoprotein B-100↗
PubMed1999

[Familial hypercholesterolemia and plasma Lp(a) levels: 2 cardiovascular risk factors].

OBJECTIVE: Lipoprotein (a) (Lp(a)) is a modified LDL particle in human plasma. Elevated Lp(a) plasma concentration has been associated with increase risk of premature heart disease in most cross-sectional studies. Familial hypercholesterolemia (FH) is a genetic disorder characterized by an elevation of LDL cholesterol (LDL-C) caused by molecular defects in the LDL receptor gene. The aim of our study is to analyze Lp(a) values in a genetic diagnosed FH group without coronary heart disease (CHD) and explain the considerable variation in clinical severity of FH patients. METHOD: We have study plasma lipids and lipoprotein levels in 60 subjects with familial hypercholesterolemia without CHD and in 74 normolipidemic controls without personal history of CHD and dyslipidemia of the Valencia area in Spain. RESULTS: We found differences in total and LDL cholesterol levels and apo B values as expected and also in plasma Lp(a) levels and log transformed values between FH subjects and normolipidemic controls (22.3 mg/dl +/- 19.4 vs 12.5 mg/dl +/- 12.6 p = 0.001 and 1.12 +/- 0.53 vs. 0.84 +/- 0.58 p = 0.008). The percentage of FH subjects with a cut point Lp(a) value > 20 mg/dl is significantly elevated in this group (47% vs 21% p = 0.002). Because of family relationships within the entire study population we also have compared 23 FH probands with the normolipidemic controls. Again the same results have been obtained (Lp(a) levels of 23.21 mg/dl +/- 19.2 vs 12.54 mg/dl +/- 12.63 p = 0.019 and log Lp(a) values of 1.19 +/- 0.42 vs 0.84 +/- 0.58 p = 0.01). CONCLUSION: Our results indicate that FH subjects will have a more cardiovascular risk due to the potentiation of hypercholesterolemia and elevated Lp(a) values, indicating the addition effects of two different locus implicated in premature coronary heart disease and could explain the considerable variation in clinical severity of FH.

Adult↗
PubMed1999

Plasma Lp(a) values in familial hypercholesterolemia and its relation to coronary heart disease.

BACKGROUND AND AIM: To analyze plasma Lp(a) levels and examine different risk factors and coronary heart disease (CHD) in a sample of genetically diagnosed familial hypercholesterolemia (FH) patients. METHODS AND RESULTS: Ninety heterozygous FH patients and 41 non-FH relatives were enrolled in a study to evaluate their plasma and lipoprotein cholesterol, as well as their triglyceride and Lp(a) levels. We found no differences in plasma Lp(a) levels and log transformed values between 90 FH subjects and their 41 unaffected relatives (22.3 mg/dl +/- 19.4 vs 17.7 mg/dl +/- 21.3 and 1.12 +/- 0.5 vs 0.96 +/- 0.54) nor between null allele and defective allele FH subjects (log Lp (a) levels 2.013 +/- 0.282 vs 1.959 +/- 0.151). FH CHD+ were significantly older, and had higher mean systolic and diastolic blood pressure and higher mean plasma triglyceride levels than FH CHD-. No differences in mean and log transformed Lp(a) plasma concentrations were found. CONCLUSIONS: Plasma Lp(a) levels are not related to LDL receptor status and class mutations, nor to the presence of CHD in FH patients.

Adult↗
PubMed1998

[Clinical and biochemical characteristics of a new case of Tangier disease in Spain].

Tangier disease (TD) is a rare autosomal recessively inherited disorder characterized by the absence or severe deficiency of high density lipoproteins (HDL) in plasma. The affected subjects have no HDL subfraction alpha-Lp A-I, which is the most important subfraction in normal HDL, and can not transform prebeta-Lp A-I subfraction in alpha-Lp A-I. In this article we describe the second homozygous patient for TD in Spain, who presented the typical clinical and biological features (hypocholesterolemia with the absence of plasmatic HDL cholesterol, hepatosplenomegaly and orange yellow tonsils) and the alterations in HDL subfractions.

Cholesterol, HDL↗