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Biomedical subjects

F Blanco-Vaca

Publications and source records attributed to F Blanco-Vaca.

At least 19 recordsLinked to original sources
PubMed2004

Emerging cardiovascular risk factors in subclinical hypothyroidism: lack of change after restoration of euthyroidism.

Subclinical hypothyroidism (SH) is a frequent condition that may be associated with increased cardiovascular risk. There is current interest in determining the effect, if any, of substitutive therapy with l-thyroxine (L-T4) on cardiovascular risk factors in SH and, particularly, on those associated with emerging cardiovacular risk, such as apolipoprotein (apo) B, lipoprotein (Lp) (a), total homocysteine (t-Hcy), and C-reactive protein (CRP). Thus, the aim of this study was to assess the impact of euthyroidism restoration on these emerging risk factors in SH. Forty-two patients diagnosed with SH were consecutively recruited before treatment. These patients were treated with L-T4 for 3 to 6 months with the dose necessary to restore euthyroidism. Lp(a), fasting and postmethionine (n = 28) t-Hcy, and CRP did not change with substitutive therapy, regardless of the respective baseline values, and the decrease in apo B paralleled that of low-density lipoprotein (LDL) cholesterol. Similarly, no treatment effect was observed on homocysteine or CRP in patients with thyrotropin-stimulating hormone (TSH) >10 mIU/L. Monitoring of emerging risk factors did not offer additional arguments for treating patients with SH and, thus, is not justified in their clinical management.

Adult↗
PubMed2001

Apo(B)-dependent dyslipidemic phenotypes in type 1 diabetic patients.

BACKGROUND: The prevalence of apo(B)-dependent dyslipidemic phenotypes, which are associated with cardiovascular disease, is increased in normocholesterolemic type 2 diabetic patients. Our aim was to determine the impact of including apo(B) in the evaluation of normocholesterolemic type 1 diabetic patients. METHODS: A total of 123 type 1 diabetic patients (47% male, age 36.6+/-12.5 years) were included. The apo(B) cut-off point (1.14 g/l) was obtained from a group of 53 normolipidemic control subjects of similar age and gender distribution; for low density lipoprotein cholesterol (LDLc), triglycerides, and high density lipoprotein cholesterol (HDLc), we used the cut-off points recommended by the National Cholesterol Education Program. LDLc was determined by ultracentrifugation or Friedewald's equation, depending on triglyceride concentrations, and apo(B) by immunoturbidimetry. RESULTS: A total of 113 (92%) type 1 diabetic patients were normocholesterolemic, and 13% of these were dyslipidemic. The frequency of hyperapo(B) was similar in normocholesterolemic patients and controls (6.2 vs. 9.4%, respectively). Diabetic patients with hyperapo(B) had poorer glycemic control, higher total cholesterol, triglycerides, and LDLc, and a lower HDLc and LDLc/apo(B) ratio. CONCLUSIONS: Unlike type 2 diabetes, type 1 diabetes is not associated with an increased prevalence of hyperapo(B)-dependent dyslipidemic phenotypes. Thus, only in patients with poor glycemic control who display other components of diabetic dyslipidemia, typical for type 2 diabetes, does determining apo(B) concentrations provide additional information in type 1 diabetes.

Journal Article↗
PubMed2001

Low-density lipoprotein particle size, triglyceride-rich lipoproteins, and glucose tolerance in non-diabetic men with essential hypertension.

The aim of the study is to investigate serum lipoproteins abnormalities including low-density lipoprotein (LDL) particle size, and their relationship with other cardiovascular risk factors in men with essential hypertension. Plasma glucose and serum insulin levels during oral glucose tolerance test (OGTT), serum lipoprotein(a), apolipoprotein (apo) A-I. apo B. cholesterol and triglycerides in serum and in lipoproteins, and LDL particle diameter were measured in thirty-eight consecutive newly-diagnosed non-diabetic untreated hypertensive men and 38 healthy male controls. Plasma glucose at baseline, 60 and 120 min during OGTT was significantly higher in patients than controls whereas serum insulin levels did not differ between patients and controls. Serum apo B and triglycerides were significantly raised in patients compared with controls (1.08 +/- 0.17 g/L [mean +/- SD] vs 0.97 +/- 0.22 g/L. p < 0.05, and 1.56 +/- 0.90 mmol/L vs 1.15 +/- 0.57 mmol/L, p < 0.05, respectively). Very-low-density lipoprotein (VLDL) triglycerides and LDL-cholesterol were increased in patients compared with controls (0.89 +/- 0.79 mmol/L and 0.54 +/- 0.35 mmol/L, p < 0.05, and 4.08 +/- 0.85 mmol/L and 3.60 +/- 0.92 mmol/L, p < 0.05, respectively) whereas high-density lipoprotein (HDL) cholesterol was lower in patients compared with controls 0.95 +/- 0.22 mmol/L and 1.07 +/- 0.20 mmol/L, p < 0.05). Adjustment for body mass index, abdominal/hip perimeter ratio and area under the glucose curve did not attenuate the relationship between hypertension and VLDL-triglycerides. Six patients and two controls had a mean LDL diameter < or = 25.5 nm and in the former serum triglycerides ranged from 1.86 mmol/L to 2.37 mmol/L. Mean LDL particle diameter in both patients and controls showed an inverse relationship with log-transformed serum triglycerides (r = - 0.51, p < 0.001 and r = - 0.47, p < 0.005, respectively). Among patients, those with serum triglycerides > or = [corrected] 1.58 mmol/L had a lesser mean LDL diameter than those with triglycerides above this threshold (25.78 +/- 0.47 nm vs 26.30 +/- 0.35 nm, p < 0.001). Higher plasma glucose, serum apo B and LDL-cholesterol as well as the decrease in serum HDL-cholesterol in patients with hypertension are consistent with high coronary heart disease risk. Not only mild hypertriglyceridemia but also high-normal serum triglycerides in themselves or as a surrogate of a predominance of small dense LDL particles in plasma convey an additional risk for cardiovascular disease in hypertensive patients even though routine plasma lipids are within or near normal range.

Adult↗
PubMed2001

ApoA-II expression in CETP transgenic mice increases VLDL production and impairs VLDL clearance.

Apolipoprotein (apo)A-II is a major high density lipoprotein (HDL) protein; however, its role in lipoprotein metabolism is largely unknown. Transgenic (Tg) mice that overexpress human apoA-II present functional lecithin: cholesterol acyltransferase deficiency, HDL deficiency, hypertriglyceridemia and, when fed an atherogenic diet, increased non-HDL cholesterol and increased susceptibility to atherosclerosis. In contrast to humans, mice do not present cholesteryl ester transfer protein (CETP) activity in plasma. To study the in vivo interaction of these two proteins, we crossbred human apoA-II and CETP-Tg mice. CETP x apoA-II-Tg mice fed an atherogenic diet, compared with CETP-Tg mice presented a 2-fold decrease in HDL cholesterol and a quantitatively similar increase in total plasma cholesterol and percentage of free cholesterol, non-HDL cholesterol, and free fatty acids, together with a remarkable 112-fold increase in plasma triglycerides. Plasma triglycerides in CETP x apoA-II-Tg mice were mainly associated with very low density lipoproteins (VLDL), which were also enriched in protein content, and resulted from a combination of higher production rate compared with both of their progenitors and non-Tg control mice, and decreased catabolism compared only with CETP-Tg mice. These results show CETP x apoA-II-Tg mice to be a good model with which to study mechanisms leading to VLDL overproduction and suggest that CETP and, in particular apoA-II, may play a role in the regulation of VLDL metabolism.

Animals↗
PubMed2001

Role of apoA-II in lipid metabolism and atherosclerosis: advances in the study of an enigmatic protein.

Our understanding of apolipoprotein A-II (apoA-II) physiology is much more limited than that of apoA-I. However, important and rather surprising advances have been produced, mainly through analysis of genetically modified mice. These results reveal a positive association of apoA-II with FFA and VLDL triglyceride plasma concentrations; however, whether this is due to increased VLDL synthesis or to decreased VLDL catabolism remains a matter of controversy. As apoA-II-deficient mice present a phenotype of insulin hypersensitivity, a function of apoA-II in regulating FFA metabolism seems likely. Studies of human beings have shown the apoA-II locus to be a determinant of FFA plasma levels, and several genome-wide searches of different populations with type 2 diabetes have found linkage to an apoA-II intragenic marker, making apoA-II an attractive candidate gene for this disease. The increased concentration of apoB-containing lipoproteins present in apoA-II transgenic mice explains, in part, why these animals present increased atherosclerosis susceptibility. In addition, apoA-II transgenic mice also present impairment of two major HDL antiatherogenic functions: reverse cholesterol transport and protection of LDL oxidative modification. The apoA-II locus has also been suggested as an important genetic determinant of HDL cholesterol concentration, even though there is a major species-specific difference between the effects of mouse and human apoA-II. As antagonizing apoA-I antiatherogenic actions can hardly be considered the apoA-II function in HDL, this remains a topic for future investigations. We suggest that the existence of apoA-II or apoA-I in HDL could be an important signal for specific interaction with HDL receptors such as cubilin or heat shock protein 60.

Animals↗
PubMed2000

Increased production of very-low-density lipoproteins in transgenic mice overexpressing human apolipoprotein A-II and fed with a high-fat diet.

We investigated the mechanisms that lead to combined hyperlipidemia in transgenic mice that overexpress human apolipoprotein (apo) A-II (line 11.1). The 11.1 transgenic mice develop pronounced hypertriglyceridemia, and a moderate increase in free fatty acid (FFA) and plasma cholesterol, especially when fed a high-fat/high-cholesterol diet. Post-heparin plasma lipoprotein lipase and hepatic lipase activities (using artificial or natural autologous substrates), the decay of plasma triglycerides with fasting, and the fractional catabolic rate of the radiolabeled VLDL-triglyceride (both fasting and postprandial) were similar in 11. 1 transgenic mice and in control mice. In contrast, a 2.5-fold increase in hepatic VLDL-triglyceride production was observed in 11. 1 transgenic mice in a period of 2 h in which blood lipolysis was inhibited. This increased synthesis of hepatic VLDL-triglyceride used preformed FFA rather than FFA of de novo hepatic synthesis. The 11.1 transgenic mice also presented reduced epididymal/parametrial white adipose tissue weight (1.5-fold), increased rate of epididymal/parametrial hormone-sensitive lipase-mediated lipolysis (1.2-fold) and an increase in cholesterol and, especially, in triglyceride liver content, suggesting an enhanced mobilization of fat as the source of preformed FFA reaching the liver. Increased plasma FFA was reverted by insulin, demonstrating that 11.1 transgenic mice are not insulin resistant. We conclude that the overexpression of human apoA-II in transgenic mice induces combined hyperlipidemia through an increase in VLDL production. These mice will be useful in the study of molecular mechanisms that regulate the overproduction of VLDL, a situation of major pathophysiological interest since it is the basic mechanism underlying familial combined hyperlipidemia.

Animals↗
PubMed2000

Genetic susceptibility to thrombosis and its relationship to physiological risk factors: the GAIT study. Genetic Analysis of Idiopathic Thrombophilia.

Although there are a number of well-characterized genetic defects that lead to increased risk of thrombosis, little information is available on the relative importance of genetic factors in thrombosis risk in the general population. We performed a family-based study of the genetics of thrombosis in the Spanish population to assess the heritability of thrombosis and to identify the joint actions of genes on thrombosis risk and related quantitative hemostasis phenotypes. We examined 398 individuals in 21 extended pedigrees. Twelve pedigrees were ascertained through a proband with idiopathic thrombosis, and the remaining pedigrees were randomly ascertained. The heritability of thrombosis liability and the genetic correlations between thrombosis and each of the quantitative risk factors were estimated by means of a novel variance component method that used a multivariate threshold model. More than 60% of the variation in susceptibility to common thrombosis is attributable to genetic factors. Several quantitative risk factors exhibited significant genetic correlations with thrombosis, indicating that some of the genes that influence quantitative variation in these physiological correlates also influence the risk of thrombosis. Traits that exhibited significant genetic correlations with thrombosis included levels of several coagulation factors (factors VII, VIII, IX, XI, XII, and von Willebrand), tissue plasminogen activator, homocysteine, and the activated protein C ratio. This is the first study that quantifies the genetic component of susceptibility to common thrombosis. The high heritability of thrombosis risk and the significant genetic correlations between thrombosis and related risk factors suggest that the exploitation of correlated quantitative phenotypes will aid the search for susceptibility genes.

Adolescent↗
PubMed2000

Determinants of plasma homocyst(e)ine in patients with nephrotic syndrome.

Hyperhomocyst(e)inemia is an independent risk factor for atherothrombosis in several clinical settings in which renal function is impaired, but its prevalence in the nephrotic syndrome has not been investigated in detail, even though this syndrome provides an excellent model in which to study a possible link between albuminuria, proteinuria, and hyperhomocyst(e)inemia. We obtained plasma and urine from 27 patients with biopsy-confirmed membranous glomerulonephritis presenting nephrotic syndrome and 27 matched controls and determined the concentrations of homocyst(e)ine and proteins considered putative markers of glomerular and tubular function. Hyperhomocyst(e)inemia, defined as the mean +SD of the plasma homocyst(e)ine concentration of the controls [plasma homocyst(e)ine concentration >10.8 micromol/l] was present in 26% of the patients with nephrotic syndrome but in only 7.4% of the controls. Furthermore, the degree of hyperhomocyst(e)inemia was more severe in the nephrotic patients than in the controls. The existence of renal failure, tubular damage, and, interestingly, relatively well conserved glomerular function barrier were the main predictors of increased levels of plasma homocyst(e)ine. In conclusion, hyperhomocyst(e)inemia is a frequent cardiovascular risk factor present in patients with nephrotic syndrome and renal failure, but it is not directly associated with proteinuria.

Adult↗
PubMed2000

Usefulness of the I/D angiotensin-converting enzyme genotype for detecting the risk of left ventricular hypertrophy in pharmacologically treated hypertensive men.

The insertion/deletion polymorphism (I/D) of the angiotensin-converting enzyme (ACE) gene has been associated in some studies with a higher prevalence of left ventricular hypertrophy (LVH), but few of them were performed on pharmacologically treated hypertensive patients. The present study was undertaken to determine whether ACE genotype determination could help in the identification of pharmacologically treated hypertensive patients at a higher risk of LVH. Ninety-six consecutive men with essential hypertension were selected for the study. Left ventricular mass (LVM) was assessed by echocardiography and indexed by body surface area and 82 patients were considered suitable for the study. Three groups of patients were defined on the basis of their I/D ACE genotype: DD (n = 39), ID (n = 33) and II (n = 10). There were no statistically significant differences between the three groups regarding to the severity of hypertension at diagnosis, degree of control of blood pressure or type of antihypertensive drug therapy used. No statistically significant differences were found between the three groups regarding to LVM index (total 124 +/- 31, DD 121 +/- 29, ID 127 +/- 35 and II 122 +/- 18 g/m2), relative wall thickness (total 0.5 +/- 0. 2, DD 0.5 +/- 0.3, ID 0.48 +/- 0.07 and II 0.47 +/- 0.04) or prevalence of LVH (total 34%, DD 31%, ID 39% and II 30% by Cornell criteria and total 39%, DD 33%, ID 45% and II 40% by Framingham criteria). Furthermore, the I and D allele frequency distribution was similar in the whole group of patients, in patients with LVH, and in a control group of healthy volunteers. Our data do not support that the I/D ACE genotype determination helps in identifying treated hypertensive patients at higher risk of LVH. Journal of Human Hypertension (2000) 14, 327-331

Adult↗
PubMed2000

Comparison of the Abbott IMx and a high-performance liquid chromatography method for measuring total plasma homocysteine.

The determination of the total concentration of plasma homocysteine is of interest in a variety of clinical circumstances, especially, in the evaluation of the risk of cardiovascular disease. However, most of the methods available to date, many of them chromatographic, are not well suited for the majority of clinical laboratories. Several automated methods are now or will be, shortly, commercially available. We have compared one of them, the fluorescence polarization immunoassay (FPIA) adapted to the IMx analyzer (Abbott Laboratories), with the high-performance liquid chromatography (HPLC) method with fluorescent detection currently used in our laboratory. The results show that the FPIA-IMx method is less imprecise and slightly more sensitive than the HPLC. The comparison of 67 clinical plasma specimens indicated that there is a proportional error disagreement between FPIA-IMx and HPLC (FPIA=1.19 HPLC + 0.92; confidence region for slope and y-intercept were, respectively, from 1.06 to 1.31 and from -0.06 to 2.32). The nature of this error is not explained by the experiments performed to study the inaccuracy of both methods, which included the investigation of dilution parallelism, analytical recovery and cross-reactivity. The different results of homocysteine concentration obtained with FPIA-IMx and HPLC must be taken into account when a change of methodology is under consideration.

Chromatography, High Pressure Liquid↗
PubMed2000

Expression of human apolipoprotein A-II in apolipoprotein E-deficient mice induces features of familial combined hyperlipidemia.

Familial combined hyperlipidemia (FCHL) is a common inherited hyperlipidemia and a major risk factor for atherothrombotic cardiovascular disease. The cause(s) leading to FCHL are largely unknown, but the existence of unidentified "major" genes that would increase VLDL production and of "modifier" genes that would influence the phenotype of the disease has been proposed. Expression of apolipoprotein A-II (apoA-II), a high density lipoprotein (HDL) of unknown function, in transgenic mice produced increased concentration of apoB-containing lipoproteins and decreased HDL. Here we show that expression of human apoA-II in apoE-deficient mice induces a dose-dependent increase in VLDL, resulting in plasma triglyceride elevations of up to 24-fold in a mouse line that has 2-fold the concentration of human apoA-II of normolipidemic humans, as well as other well-known characteristics of FCHL: increased concentrations of cholesterol, triglyceride, and apoB in very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL) and low density lipoprotein (LDL), reduced HDL cholesterol, normal lipoprotein lipase and hepatic lipase activities, increased production of VLDL triglycerides, and increased susceptibility to atherosclerosis. However, FCHL patients do not have plasma concentrations of human apoA-II as high as those of apoE-deficient mice overexpressing human apoA-II, and the apoA-II gene has not been linked to FCHL in genome-wide scans. Therefore, the apoA-II gene could be a "modifier" FCHL gene influencing the phenotype of the disease in some individuals through unkown mechanisms including an action on a "major" FCHL gene. We conclude that apoE-deficient mice overexpressing human apoA-II constitute useful animal models with which to study the mechanisms leading to overproduction of VLDL, and that apoA-II may function to regulate VLDL production.

Animals↗
PubMed1999

Effect of simvastatin treatment on the electronegative low-density lipoprotein present in patients with heterozygous familial hypercholesterolemia.

Most described modifications of low-density lipoprotein (LDL) cholesterol share an increase in its negative electric charge; in fact, an electronegative form of LDL can be identified and isolated from plasma. Although the exact nature of the chemical modification of electronegative LDL is still controversial, its toxicity on endothelial cells has been demonstrated. Statins have protective effects against cardiovascular disease that are independent of their lipid-lowering action and which could be due, at least in part, to the prevention of LDL modification. We evaluated the effect of 6 months of simvastatin therapy (40 mg/day) on electronegative LDL proportion and LDL susceptibility to in vitro induced oxidation in 21 patients with heterozygous familial hypercholesterolemia (FH). Eleven normolipemic subjects were analyzed as a control group. Total cholesterol as well as LDL and very low density lipoprotein cholesterol, triglycerides, and apoprotein B decreased 30% after the first month of therapy, with no further decreases thereafter. LDL susceptibility to oxidation was similar in FH patients and controls and did not change throughout the treatment. Electronegative LDL proportion was 35.1 +/- 9.9% in FH patients and 9.1 +/- 2.4% in control subjects (p <0.0001) but, in contrast to total LDL cholesterol and the rest of lipid parameters, it decreased to 28.6 +/- 9.1% in the third month and to 21.2 +/- 7.7% in the sixth month of therapy. The decrease in these cytotoxic particles may be a relevant mechanism by which simvastatin protects against cardiovascular disease.

Adult↗