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Biomedical subjects

Emilio Ros

Publications and source records attributed to Emilio Ros.

At least 19 recordsLinked to original sources
PubMed2006

Effects of a Mediterranean-style diet on cardiovascular risk factors: a randomized trial.

BACKGROUND: The Mediterranean diet has been shown to have beneficial effects on cardiovascular risk factors. OBJECTIVE: To compare the short-term effects of 2 Mediterranean diets versus those of a low-fat diet on intermediate markers of cardiovascular risk. DESIGN: Substudy of a multicenter, randomized, primary prevention trial of cardiovascular disease (Prevención con Dieta Mediterránea [PREDIMED] Study). SETTING: Primary care centers affiliated with 10 teaching hospitals. PARTICIPANTS: 772 asymptomatic persons 55 to 80 years of age at high cardiovascular risk who were recruited from October 2003 to March 2004. INTERVENTIONS: Participants were assigned to a low-fat diet (n = 257) or to 1 of 2 Mediterranean diets. Those allocated to Mediterranean diets received nutritional education and either free virgin olive oil, 1 liter per week (n = 257), or free nuts, 30 g/d (n = 258). The authors evaluated outcome changes at 3 months. MEASUREMENTS: Body weight, blood pressure, lipid profile, glucose levels, and inflammatory molecules. RESULTS: The completion rate was 99.6%. Compared with the low-fat diet, the 2 Mediterranean diets produced beneficial changes in most outcomes. Compared with the low-fat diet, the mean changes in the Mediterranean diet with olive oil group and the Mediterranean diet with nuts group were -0.39 mmol/L (95% CI, -0.70 to -0.07 mmol/L) and -0.30 mmol/L (CI, -0.58 to -0.01 mmol/L), respectively, for plasma glucose levels; -5.9 mm Hg (CI, -8.7 to -3.1 mm Hg) and -7.1 mm Hg (CI, -10.0 to -4.1 mm Hg), respectively, for systolic blood pressure; and -0.38 (CI, -0.55 to -0.22) and - 0.26 (CI, -0.42 to -0.10), respectively, for the cholesterol-high-density lipoprotein cholesterol ratio. The Mediterranean diet with olive oil reduced C-reactive protein levels by 0.54 mg/L (CI, 1.04 to 0.03 mg/L) compared with the low-fat diet. LIMITATIONS: This short-term study did not focus on clinical outcomes. Nutritional education about low-fat diet was less intense than education about Mediterranean diets. CONCLUSION: Compared with a low-fat diet, Mediterranean diets supplemented with olive oil or nuts have beneficial effects on cardiovascular risk factors.

Aged↗
PubMed2006

Influence of HDL cholesterol on preclinical carotid atherosclerosis in familial hypercholesterolemia.

OBJECTIVE: The effect of risk factors on carotid atherosclerosis in heterozygous familial hypercholesterolemia (FH) is unclear. We evaluated carotid intima-media thickness (IMT) by sonography in relation to classical and emergent risk factors in a large FH cohort. METHODS AND RESULTS: Risk factors and carotid IMT were assessed in 196 asymptomatic subjects aged > or =25 years fulfilling strict diagnostic criteria for clinical FH who were either undertreated or treatment-naive. Conventional risk factors, but not lipoprotein(a), homocysteine, or apolipoprotein E (apoE) genotypes were univariately related to IMT. Age-adjusted and gender-adjusted IMT increased with increasing low-density lipoprotein (LDL) cholesterol and decreased with increasing high-density lipoprotein (HDL) cholesterol. Compared with a total cholesterol/HDL ratio >5.0, a ratio < or =5.0 was associated with a lower adjusted IMT, with a mean difference of -0. 09 mm (95% confidence interval, -0.13 to -0.04). By multivariate analysis, age, HDL cholesterol (negatively), physical exercise, family history of early-onset coronary heart disease, LDL cholesterol, and leukocyte count, in this order, were independent associations of IMT (r2=0.429, P<0.001). CONCLUSIONS: Traditional risk factors account for a sizeable proportion of variation in carotid IMT in FH. Because the HDL cholesterol level and the total cholesterol/HDL ratio are strong predictors of preclinical carotid atherosclerosis, HDL cholesterol-raising strategies should have an important therapeutic role in FH.

Adult↗
PubMed2005

[Carotid ultrasound in the assessment of preclinical atherosclerosis. Distribution of intima-media thickness values and plaque frequency in a Spanish community cohort].

BACKGROUND AND OBJECTIVE: High-resolution B-mode ultrasound measurements of carotid intima-media thickness (IMT) and determination of plaque presence are useful to assess preclinical atherosclerosis. Normal IMT values have not been reported in Spanish subjects. Our aim was to define normality data of carotid ultrasound by sex and age. SUBJECTS AND METHODS: We studied 250 healthy, normolipidemic subjects, 125 men and 125 women, with mean age 49 years (range, 20-81). We assessed cardiovascular risk factors and performed ultrasound determination of mean and maximum IMT in the far wall of the common carotid artery, plaque occurrence, and maximum plaque height. RESULTS: Reference values for carotid IMT, expressed as 25th, 50th, and 75th percentiles by sex and 5 age groups, have been obtained. The 50th percentiles of mean IMT ranged from 0.50 to 0.74 mm in men in the age groups 35 years or younger and 65 years or older, respectively. For women, corresponding IMT values ranged from 0.40 to 0.65 mm. IMT was strongly related (p < 0.001) to age, both in men (r = 0.57) and women (r = 0.61). From the regression equations, the estimated yearly increase in IMT was 0.005 mm in men and 0.007 mm in women. More than 50% of men aged 55 years and older, and of women aged 65 years and older, had carotid plaques. CONCLUSIONS: Both IMT and plaque frequency were associated with age in men and women. Carotid IMT values in a Spanish community cohort were lower than those reported for countries with higher cardiovascular risk, such as Northern European countries and the US.

Adult↗
PubMed2005

The use of Achilles tendon sonography to distinguish familial hypercholesterolemia from other genetic dyslipidemias.

OBJECTIVE: Achilles tendon (AT) xanthomas, specific for familial hypercholesterolemia (FH), may be clinically undetectable. We assessed the usefulness of AT sonography in the diagnosis of FH. METHODS AND RESULTS: Sonographic AT characteristics were evaluated in 127 subjects with FH (81 genetically ascertained), 84 familial combined hyperlipidemia, 79 polygenic hypercholesterolemia, and 88 normolipidemic controls. Abnormal echostructure (sonographic xanthoma) was noted only in FH. AT thickness was higher (P<0.001) in FH men and women compared with all of the other groups and, in FH mutation carriers but not in others, correlated positively with low-density lipoprotein cholesterol (r=0.345; P<0.001) and negatively with high-density lipoprotein cholesterol (r=-0.265, P=0.015). Thickness thresholds for the diagnosis of FH with specificity >80%, as were derived from receiver operating curves, were 5.3 and 5.7 mm in men < and >45 years, and 4.8 and 4.9 mm in women < and >50 years, respectively. In FH mutation carriers, sonographic findings increased the clinical diagnosis of xanthomas from 35 (43%) to 55 (68%). Using thresholds in validation sets of 70 genetically identified FH and 54 dyslipidemic non-FH correctly classified 80% and 88%, respectively. CONCLUSIONS: Sonographic AT characteristics are normal in non-FH dyslipidemias. Identification of suspected FH by ultrasound using sex- and age-specific AT thickness thresholds is recommended.

Achilles Tendon↗
PubMed2005

Tendon xanthomas in familial hypercholesterolemia are associated with cardiovascular risk independently of the low-density lipoprotein receptor gene mutation.

OBJECTIVE: To investigate the significance of tendon xanthomas (TX) in heterozygous subjects with familial hypercholesterolemia (hFH). METHODS AND RESULTS: 951 men and women with genetic diagnosis of hFH were studied, of whom 278 (29.2%) presented TX. TX frequency increased with age from 6.9% in subjects 20 to 30 years to 38.3% at 51 to 60 years, with a decrease in those older than 60 years. Total and low-density lipoprotein (LDL) cholesterol were higher in TX+ than in TX- subjects (439.0+/-78.5 mg/dL and 363.1+/-76.5 mg/dL versus 400.6+/-73.4 and 323.3+/-71.0, respectively; P=0.001). High-density lipoprotein (HDL) cholesterol was lower in TX+ than in TX- subjects (50.4+/-15.0 mg/dL versus 53.1+/-14.8 mg/dL; P=0.005). Lp(a), apolipoprotein E genotype, and type of LDL receptor gene mutation showed no differences between groups. 102 TX+ reported premature cardiovascular disease (CVD) (36.7%) versus 93 TX- (13.8%) (P=0.001). The relative odds for premature CVD were higher in women (4.49 versus 2.26), and increased in hFH younger than 51 years to 3.60 (95% CI, 1.703 to 7.608) in men and to 17.1 (95% CI, 2.697 to 108.920) in women. In the multivariate analysis, age, male sex, LDL cholesterol, and hypertension showed significant positive association with TX, whereas body mass index showed negative association with TX. CONCLUSIONS: TX are associated with cardiovascular risk factors and higher CVD, indicating that their detection indicates the need for more aggressive lipid-lowering intervention.

Adult↗
PubMed2005

Preclinical vascular disease in systemic lupus erythematosus and primary antiphospholipid syndrome.

OBJECTIVE: To determine the prevalence of preclinical vascular disease and associated risk factors in patients with systemic lupus erythematosus (SLE) or primary antiphospholipid syndrome (APS). METHODS: We consecutively studied 70 SLE patients and 25 primary APS patients without clinical coronary artery disease. The control group included 40 healthy women. Carotid ultrasound was performed and the intima-media wall thickness (IMT) and presence of plaque was investigated in all patients and controls. Traditional vascular risk factors and SLE-disease and treatment related factors were also analysed. RESULTS: SLE patients had a higher prevalence of traditional atherosclerosis risk factors: hypertension (P<0.005) and dyslipidaemia (P<0.05) and higher levels of total cholesterol (P = 0.03), triglycerides (P = 0.004) and apolipoprotein B (P = 0.04). The prevalence of carotid plaque was higher and appeared earlier in SLE patients than in the primary APS patients or controls (P<0.001). The IMT was similar in the three groups. SLE patients with secondary APS had a higher prevalence of carotid plaque than patients with primary APS (37.5% vs 8%, P = 0.03). The presence of plaque in SLE patients was associated with a higher SLICC score (2.40 +/- 1.78 vs 1.02 +/- 1.18, P = 0.002), higher ECLAM score (3.10 +/- 2.32 vs 1.84 +/- 1.59, P = 0.02) and older age (47.3 +/- 8.44 vs 37.38 +/- 11.28, P = 0.003) at the time of carotid ultrasound study. CONCLUSION: Plaque prevalence in patients with primary APS is similar to that of controls and inferior to that of SLE patients with secondary APS. SLE patients have a high prevalence of early carotid atherosclerosis that is associated with cumulative disease damage and disease activity.

Adult↗
PubMed2005

Nonalcoholic fatty liver disease is associated with carotid atherosclerosis: a case-control study.

OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD) frequently coexists with obesity, diabetes, and dyslipidemia. We examined whether NAFLD was associated with atherosclerosis, as measured by ultrasound in the carotid arteries. METHODS AND RESULTS: Carotid atherosclerosis and cardiovascular risk factors were assessed in 40 patients with an ultrasound diagnosis of primary NAFLD and 40 matched population controls. The metabolic syndrome and all its individual traits, including elevated C-reactive protein, were significantly (P<0.005) more frequent in NAFLD patients than in control subjects. Patients with NAFLD showed more carotid atherosclerosis than controls, with mean intima-media thickness (IMT) of 0.70+/-0.20 mm and 0.54+/-0.13 mm (P<0.0001) and plaque prevalence of 50% and 25% (P=0.021), respectively. By multivariate analysis, older age (odds ratio [OR], 2.5 per 10 years; 95% CI, 1.4 to 4.4; P=0.002), the presence of NAFLD (OR, 8.4; 95% CI, 2.49 to 29.4; P=0.001), and elevated serum ferritin (OR, 3.1; 95% CI, 1.2 to 7.9; P=0.016) were independent predictors of an increased IMT. CONCLUSIONS: Patients with NAFLD show a cluster of risk factors of the metabolic syndrome and advanced carotid atherosclerosis. NAFLD appears to be a feature of the metabolic syndrome, and its detection on abdominal ultrasound should alert to the existence of an increased cardiovascular risk.

Adult↗
PubMed2004

[Hypertriglyceridemic acute pancreatitis. Is its clinical course different from lithiasic acute pancreatitis?].

BACKGROUND AND OBJECTIVE: Although hypertriglyceridemia is an accepted cause of acute pancreatitis, its clinical course is not well defined. What is more, lipemic serum may interfere with an accurate pancreatic enzyme measurement and may hinder the diagnosis of acute pancreatitis. The objective was to analyze the clinical performance of hypertriglyceridemic acute pancreatitis and the diagnosis value of the serum measurement of pancreatic enzymes. PATIENTS AND METHOD: 31 demographic, clinical, analytical and radiological data of 19 hypertriglyceridemic acute pancreatitis were retrospectively analyzed and their results were compared with data of 19 lithiasic acute pancreatitis without hypertriglyceridemia. Diagnosis of acute pancreatitis was based on clinical, radiological and/or laparotomical findings. Serum levels of triglycerides higher than 1,000 mg/dl were considered the cause of acute pancreatitis when other causes were excluded. Acute pancreatitis was considered lithiasic when gallstones were identified by ultrasonography, serum levels of triglycerides were lower than 200 mg/dl and there was no history of alcohol consumption. RESULTS: Compared with lithiasic acute pancreatitis, hypertriglyceridemic acute pancreatitis showed more personal and family hypertriglyceridemia (9 vs 0), more previous episodes of pancreatitis (13 vs 2), pancreatitis was more severe (13 vs 5) and had more complications (29 vs 5). There was no mortality in either group. The serum levels of amylase and lipase supported the diagnosis in 26% and 58% of patients with hypertriglyceridemic acute pancreatitis compared with 58% and 79% of patients with lithiasic acute pancreatitis, respectively. Hospital stay was longer in hypertriglyceridemic than in lithiasic acute pancreatitis (24 [45] vs 7.6 [3.1] days; p = NS). Demographic and analytical factors which could permit to predict the severity of acute pancreatitis could not be identified. CONCLUSIONS: Hypertriglyceridemic acute pancreatitis is relapsing and its clinical course is more severe than lithiasic acute pancreatitis. The measurement of amylase and lipase levels is less useful in the diagnosis of hypertriglyceridemic than in lithiasic acute pancreatitis.

Acute Disease↗
PubMed2004

Treatment of type IIb familial combined hyperlipidemia with the combination pravastatin-piperazine sultosilate.

The risk of coronary heart disease is increased for any given low-density lipoprotein (LDL) cholesterol level in patients with high levels of triglycerides because some triglyceride-rich lipoproteins are atherogenic. This paper reports the results of a pilot clinical trial aimed to evaluate a novel triglyceride-lowering drug in combination with pravastatin to treat combined hyperlipidemia. Twenty-six patients with type 2b hyperlipoproteinemia were randomized to receive pravastatin 40 mg/day or pravastatin 40 mg/day plus piperazine-sultosilate 1000 mg/day for 12 weeks if their cholesterol levels, but not triglyceride levels, had responded to therapeutic lifestyle changes and treatment with 40 mg/day of pravastatin. Concentrations of triglycerides, cholesterol and apolipoproteins A and B were measured in duplicate before and after the intervention. There were no significant differences between groups in the change from baseline in the concentration of serum triglycerides. Conversely, significant differences were found for LDL cholesterol, which increased slightly with pravastatin alone but decreased with the combination (12.605+/-22.777% vs. -6.396+/-13.157%, respectively; p=0.022). Apolipoprotein-B levels increased with pravastatin alone but remained stable with the combined treatment (10.464+/-8.446% vs. 0.767+/-12.335%; P=0.028). The increase in the pravastatin group was significant. Although sultosilate was not efficacious in reducing triglycerides, it helped to decrease the concentration of small, dense, atherogenic LDL particles that are less receptor-sensitive and which could accumulate during long-term statin therapy in patients with high levels of triglycerides.

Adolescent↗
PubMed2004

A walnut diet improves endothelial function in hypercholesterolemic subjects: a randomized crossover trial.

BACKGROUND: Epidemiological studies suggest that nut intake decreases coronary artery disease (CAD) risk. Nuts have a cholesterol-lowering effect that partly explains this benefit. Endothelial dysfunction is associated with CAD and its risk factors and is reversed by antioxidants and marine n-3 fatty acids. Walnuts are a rich source of both antioxidants and alpha-linolenic acid, a plant n-3 fatty acid. METHODS AND RESULTS: To test the hypothesis that walnut intake will reverse endothelial dysfunction, we randomized in a crossover design 21 hypercholesterolemic men and women to a cholesterol-lowering Mediterranean diet and a diet of similar energy and fat content in which walnuts replaced approximately 32% of the energy from monounsaturated fat. Participants followed each diet for 4 weeks. After each intervention, we obtained fasting blood and performed ultrasound measurements of brachial artery vasomotor function. Eighteen subjects completing the protocol had suitable ultrasound studies. Compared with the Mediterranean diet, the walnut diet improved endothelium-dependent vasodilation and reduced levels of vascular cell adhesion molecule-1 (P<0.05 for both). Endothelium-independent vasodilation and levels of intercellular adhesion molecule-1, C-reactive protein, homocysteine, and oxidation biomarkers were similar after each diet. The walnut diet significantly reduced total cholesterol (-4.4+/-7.4%) and LDL cholesterol (-6.4+/-10.0%) (P<0.05 for both). Cholesterol reductions correlated with increases of both dietary alpha-linolenic acid and LDL gamma-tocopherol content, and changes of endothelium-dependent vasodilation correlated with those of cholesterol-to-HDL ratios (P<0.05 for all). CONCLUSIONS: Substituting walnuts for monounsaturated fat in a Mediterranean diet improves endothelium-dependent vasodilation in hypercholesterolemic subjects. This finding might explain the cardioprotective effect of nut intake beyond cholesterol lowering.

Adult↗
PubMed2003

Fibrates modify the expression of key factors involved in bile-acid synthesis and biliary-lipid secretion in gallstone patients.

AIMS: Fibrate treatment induces adverse changes in biliary-lipid and bile-acid composition. Since the molecular mechanisms underlying these changes are still unclear, we have investigated the effect of fibrate treatment on key factors involved in bile-acid synthesis, biliary-lipid secretion and cholesterol metabolism in gallstone patients. METHODS: Patients with uncomplicated gallstones and a serum level of low-density lipoprotein (LDL) cholesterol >130 mg/dl were randomly assigned to open-label treatment with bezafibrate, fenofibrate, gemfibrozil, or placebo for 8 weeks before elective cholecystectomy. A liver specimen was obtained at operation, and the mRNA relative levels for cholesterol 7alpha-hydroxylase (CYP7A1), hepatocyte nuclear factor-4 (HNF-4), ATP-binding cassette transporters MDR3, ABCG5, and ABCG8, human homologue scavenger receptor BI, sterol response element binding protein-2 (SREBP-2), 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase and LDL receptor were determined by means of reverse-transcriptase polymerase chain reaction. RESULTS: Bezafibrate, fenofibrate and gemfibrozil significantly reduced CYP7A1 mRNA levels. The three fibrates tested raised the mRNA levels of ABCG5 and SREBP-2, but only bezafibrate induced significant changes. Although MDR-3 mRNA levels were slightly increased by the three fibrates, no significant differences were obtained. CONCLUSIONS: These results show for the first time that fibrate administration to humans downregulates CYP7A1. Although ABCG5 and SREBP-2 mRNA levels were slightly increased by all treatment groups, only bezafibrate induced significant changes.

Bezafibrate↗
PubMed2003

Utility of ambulatory 24-hour esophageal pH and motility monitoring in noncardiac chest pain: report of 90 patients and review of the literature.

It is unclear whether prolonged motility monitoring improves the diagnostic yield of standard esophageal tests in patients with noncardiac chest pain. Our aim was to assess the diagnostic value of ambulatory 24-hr pH and pressure monitoring in patients with noncardiac chest pain. Stationary manometry, edrophonium testing, and ambulatory pH and motility studies were performed in 90 consecutive patients with recurrent chest pain and normal coronary angiograms. Normality limits of ambulatory 24-hr motility were established in 30 healthy controls. The diagnoses of specific esophageal motility disorders (nutcracker esophagus and diffuse esophageal spasm) by stationary and ambulatory manometry were discordant in 48% of the patients. Edrophonium testing was positive in 9 patients, but correlated poorly with esophageal diagnoses. During ambulatory studies, 144 chest pain events occurred in 42 patients, and 72 (50%) were related to esophageal dysfunction. Strict temporal associations of events with esophageal dysfunction in relation to ambulatory 24-hr pH/motility scores permitted four patient categorizations: true positives (event-related and abnormal tests), N = 15; true negatives (event-unrelated and abnormal tests), N = 10; reduced esophageal pain threshold (event-related and normal tests), N = 4; and indeterminate origin (event-unrelated and normal tests), N = 13. Overall, 19 patients (21%) had a probable esophageal cause for chest pain (14 esophageal motility disorder, 4 acid reflux, 1 both). In conclusion, ambulatory manometry increases the diagnostic yield of standard esophageal testing in noncardiac chest pain, but the gain is small. Causes of chest pain other than high esophageal pressures and acid reflux must still be sought in most patients with chest pain of unknown origin after a negative cardiac work-up.

Adult↗
PubMed2003

Reductions in plasma cholesterol levels after fenofibrate treatment are negatively correlated with resistin expression in human adipose tissue.

The adipocyte-derived cytokine, resistin, has been proposed as the link between obesity and type 2 diabetes mellitus in murine models. In humans, resistin is identical to FIZZ3 (found in inflammatory zone 3), which belongs to a family of proteins that appears to be involved in inflammatory processes. To study the mechanisms by which fibrates improve glucose homeostasis, we determined resistin mRNA levels by using relative quantitative reverse-transcriptase-polymerase chain reaction (RT-PCR) in omental white adipose tissue samples obtained from patients treated with placebo or fenofibrate (200 mg/d) for 8 weeks before elective cholecystectomy. Fenofibrate treatment reduced total plasma cholesterol and low-density lipoprotein (LDL)-cholesterol levels by 24% and 35%, respectively. Compared with placebo values, a 2.4-fold induction in resistin mRNA levels was observed in white adipose tissue of fenofibrate-treated patients, whereas no changes were observed in the mRNA levels of the well-known perosixome proliferator-activated receptor (PPAR) target genes CD36, acyl-CoA oxidase, and carnitine palmitoyltransferase. These findings indicate that resistin changes were not related to PPAR activation by fenofibrate. Interestingly, resistin mRNA levels showed a negative correlation with plasma cholesterol levels (r2 =.53, P =.039, n = 8), but not with triglyceride levels (r2 =.02, P =.73, n = 8). These results suggest that cholesterol regulates resistin expression in human white adipose tissue.

Acyl-CoA Oxidase↗
PubMed2003

Dietary cis-monounsaturated fatty acids and metabolic control in type 2 diabetes.

Whether low-fat, high-carbohydrate (CHO) diets or moderately high-fat, high-monounsaturated fatty acid (MUFA) diets are preferable for the treatment and prevention of diabetes has been a matter of debate. High-fat diets based on MUFA-rich oils or whole foods have been compared with high-CHO diets for effects on several cardiovascular risk outcomes in diabetic subjects. Early studies using metabolic diets with wide differences in total fat content (15-25% of energy) generally found a beneficial effect of MUFA diets on glycemic control and serum lipids. Recent studies using prescribed diets with a difference of </= 15% of energy in total fat between low-fat and high-MUFA diets show similar effects on glycemic profiles but still favor MUFA diets for effects on triacylglycerols and HDL cholesterol. It is unclear whether postprandial fat clearance is impaired by CHO diets and improved by MUFA diets, independent of effects on fasting triacylglycerol concentrations. Unless one diet contains abundant antioxidants, the 2 dietary approaches appear to have similar effects on LDL oxidation. Low-fat diets, however, are associated with atherogenic, dense LDL particles, while normal, buoyant LDL predominate with high-fat diets irrespective of fatty acid composition. Limited experimental evidence suggests that MUFA diets favorably influence blood pressure, coagulation, endothelial activation, inflammation, and thermogenic capacity. Energy-controlled high-MUFA diets do not promote weight gain and are more acceptable than low-fat diets for weight loss in obese subjects. Thus, there is good scientific support for MUFA diets as an alternative to low-fat diets for medical nutrition therapy in diabetes.

Clinical Trials as Topic↗
PubMed2002

Effect of atorvastatin and bezafibrate on plasma levels of C-reactive protein in combined (mixed) hyperlipidemia.

C-reactive protein (CRP) is a non-specific but sensitive marker of underlying systemic inflammation. High CRP plasma levels correlate with risk for future cardiovascular events. The present study evaluated the effects of atorvastatin (10-40 mg) and bezafibrate (400 mg) on CRP concentrations after 6 and 12 months of treatment in 103 patients with combined (mixed) hyperlipidemia. The number of cardiovascular risk factors present in a given patient was associated with baseline CRP levels. After 6 months and 1 year, atorvastatin treatment was associated with significant (P<0.001) decreases from baseline of CRP concentrations by 29 and 43%, respectively, while bezafibrate-treated patients showed non-significant reductions of 2.3 and 14.6%, respectively (P=0.056 and 0.005 for the respective differences between the two treatment arms at 6 months and 1 year). The magnitude of change in CRP after 1 year was directly related to baseline CRP levels. Covariance analysis showed that CRP decreases in the atorvastatin group were unrelated to total cholesterol and LDL cholesterol reductions; however, they were directly related to triglyceride changes (r=0.28, P=0.047) and inversely related to HDL cholesterol changes (r=-0.28, P=0.045). A model including baseline CRP values and treatment effect showed that atorvastatin use was a significant predictor of change in CRP levels over time (beta=0.82, P=0.023). These results suggest a potential anti-atherosclerotic additional benefit of atorvastatin in patients at a risk of cardiovascular disease.

Adult↗
PubMed2002

The apolipoprotein B R3500Q gene mutation in Spanish subjects with a clinical diagnosis of familial hypercholesterolemia.

Familial hypercholesterolemia (FH) and familial defective apolipoprotein B-100 (FDB) are autosomal codominant diseases characterized by elevated LDL cholesterol levels and premature coronary artery disease. Mutations of the LDL-receptor and apolipoprotein B genes, which affect the binding domains of their protein products, are the causal defects. Securing the diagnosis of these conditions by molecular assays is important because it mandates early intervention for coronary risk reduction. DNA screening for apolipoprotein B R3500Q gene mutation was performed in 913 unrelated Spanish individuals with a clinical diagnosis of FH using a modified polymerase chain reaction protocol and restriction enzyme genotyping. Thirteen FDB heterozygotes were identified (frequency of 1.4% in subjects with a clinical diagnosis of FH). The prevalence of hypercholesterolemic subjects with FDB in the general Spanish population was estimated to be as low as 2.8 x 10(-5) (95% CI, -3.1 x 10(-4) to 3.7 x 10(-4)). The ancestors of 11 out of 13 FDB carriers were from Galicia, a region of Celtic ancestry in Northwestern Spain. As the series included 100 unrelated subjects of Galician ancestry, FDB appears to be an important genetic cause of hypercholesterolemia in this region. All the R3500Q mutations were found on the same allele, assigned to haplotype XbaI-/MspI+/EcoRI-/3HVR48, suggesting that the mutant alleles are identical by descent in people from Spain, as observed in other Caucasian populations. In conclusion, the R3500Q mutation of the apolipoprotein B gene, a common cause of FH in central Europe, is infrequent in the general Spanish population, but it is common in Galicia.

Adult↗
PubMed2002

Fibrate treatment does not modify the expression of acyl coenzyme A oxidase in human liver.

BACKGROUND AND OBJECTIVES: Fibrates induce hepatic peroxisome proliferation and carcinogenesis in rodents by activating peroxisome proliferator-activated receptor alpha (PPAR(alpha)). There is no conclusive evidence that humans are unresponsive to peroxisome proliferation, and concern exists about the long-term safety of fibrate treatment. METHODS: In a university hospital setting, 48 patients with uncomplicated gallstones and a serum level of low-density lipoprotein cholesterol greater than 130 mg/dL were randomly assigned to open-label treatment with bezafibrate (400 mg/d), fenofibrate (200 mg/d), gemfibrozil (900 mg/d), or placebo for 8 weeks before elective cholecystectomy. Serum samples for lipid determinations were obtained at baseline and before surgery. A liver specimen was obtained at operation, and the relative levels of messenger ribonucleic acid (mRNA) for the wild and truncated forms of PPAR(alpha), acyl coenzyme A oxidase, liver carnitine palmitoyltransferase I, apolipoprotein A-I, and stearoyl coenzyme A desaturase were determined. RESULTS: Fenofibrate, bezafibrate, and gemfibrozil reduced plasma low-density lipoprotein cholesterol levels by 22% (P =.009), 14% (P =.042), and 11% (not significant), respectively. Plasma triglyceride levels decreased significantly (24%-36%; P <.05), whereas high-density lipoprotein cholesterol levels rose nonsignificantly after treatment with the 3 fibrates. Except for a 35% increase of apolipoprotein A-I mRNA after fenofibrate administration (P <.05), none of the individual fibrates induced significant changes in the mRNAs tested, although as a group they increased the mRNA for liver carnitine palmitoyltransferase I by 40%(P =.08; marginally significant). CONCLUSIONS: Fibrate administration to humans at pharmacologic doses able to activate PPAR(alpha) and to induce a hypolipidemic effect does not increase the hepatic expression of acyl coenzyme A oxidase, a well-known marker of peroxisome proliferation in rodents.

Acyl-CoA Oxidase↗