Juan Rubiés-Prat

Lipoprotein and apolipoprotein profile in men with ischemic stroke. Role of lipoprotein(a), triglyceride-rich lipoproteins, and apolipoprotein E polymorphism.

Background and Purpose: The role of lipoprotein abnormalities in the development of ischemic cerebrovascular disease has not been sufficiently clarified. The aim of this study was to identify the lipoprotein profile in ischemic cerebrovascular disease and the possible role of apolipoprotein E polymorphism. Methods: The relation between the concentrations of lipoprotein(a), intermediate density lipoproteins, apolipoprotein A-I, apolipoprotein B, apolipoprotein E, and other lipoproteins was studied in 100 men with ischemic cerebrovascular disease (48 atherothrombotic, 28 lacunar, and 24 of unknown type) and in 100 healthy age-matched men as a control group. Results: Patients with ischemic cerebrovascular disease had significantly higher levels of lipoprotein (a), lipids carried by intermediate density lipoproteins, and low density lipoprotein cholesterol and lower levels of high density lipoproteins than control subjects. Patients with atherothrombotic infarction had higher total serum cholesterol and low density lipoprotein cholesterol concentrations than patients with lacunar infarction. To assess lipoprotein abnormalities in normolipidemic subjects, a subgroup of 38 patients with ischemic cerebrovascular disease and 53 control subjects, both with serum cholesterol levels <5.2 mmol/1 (200 mg/dl) and triglycerides <2.3 mmol/1 (200 mg/dl), was analyzed. Serum lipoprotein (a), lipids carried by very low density lipoproteins and intermediate density lipoproteins, and low density lipoprotein triglycerides were significantly higher in normolipidemic patients compared with normolipidemic control subjects, whereas high density lipoprotein cholesterol levels were lower. Apolipoprotein E polymorphism in our ischemic cerebrovascular patients differed from that of the control group, with the ϵ4 allele being more prevalent. Conclusions: Increased serum lipoprotein (a) levels and intermediate density lipoprotein abnormalities together with decreased high density lipoprotein levels are major risk factors for ischemic cerebrovascular disease, even in normocholesterolemic and normotriglyceridemic subjects. Finally, the ϵ4 allele could probably be a predisposing genetic marker for ischemic cerebrovascular disease.

Bone remodelling in human immunodeficiency virus-1-infected patients. A histomorphometric study

The aim of this study was to identify and describe possible alterations of bone histomorphometry in patients with human immunodeficiency virus (HIV-1) infection and to assess the relation between these alterations and disease severity. Forty-four HIV-1-infected patients seen successively at our hospital were evaluated for the study. In an attempt to avoid confounding factors as far as possible, we excluded patients who fulfilled any of the following criteria: age less than 18 or greater than 40 years; recent history of extended bed rest; previous diagnosis of metabolic bone disease, renal insufficiency, or hepatic failure; clinical or echographic signs of liver cirrhosis; diabetes mellitus or previous diagnosis of other endocrine diseases; drug therapy that could act on bone metabolism; and/or moderate to severe nutritional alteration. Twenty-two patients (13 men, 9 women; age: 27.9 +/- 4.1 years, mean +/- standard deviation) were included in the study. Plasma and urine biochemistry and calcium-regulating hormones were determined. Bone mineral content was measured on vertebrae L2 to L4 and on the neck and intertrochanteric areas of the femur by dual-photon absorptiometry. A transiliac bone biopsy was performed after double-tetracycline labelling, with histomorphometric study of undecalcified bone. Serum osteocalcin was found to be lower in patients who, according to the Centers for Disease Control (CDC) classification, had greater disease severity, and showed a positive correlation with the number of CD4+ T lymphocytes. No alterations in bone densitometry were observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Calculated Low-Density Lipoprotein Cholesterol Should Not Be Used for Management of Lipoprotein Abnormalities in Patients With Diabetes Mellitus

OBJECTIVE To assess the validity of calculated low-density lipoprotein cholesterol by the Friedewald formula for management of lipoprotein abnormalities in patients with diabetes mellitus. RESEARCH DESIGN AND METHODS Calculated LDL cholesterol by the Friedewald formula was compared with measured LDL cholesterol after separation by ultracentrifugation in 61 patients with type I diabetes, 50 patients with type II diabetes, and 116 healthy control subjects. RESULTS Calculated LDL cholesterol coincided with measured LDL cholesterol, with < 10% error, in 54 (49%) patients with diabetes mellitus, and 85 (73%) control subjects. Calculated LDL cholesterol was overestimated, with an error of > or = 10% of measured LDL cholesterol in 39% of patients and 26% of control subjects, and underestimated in 13 and 1%, respectively. Despite a good correlation between calculated and measured LDL cholesterol, the intraclass correlation coefficients demonstrated a poor concordance between calculated and measured LDL cholesterol, both in patients and control subjects. When comparing the mean differences of calculated and measured LDL cholesterol for diabetic subjects versus control subjects, significantly greater differences in type II (but not type I) diabetic subjects were seen. CONCLUSIONS Calculation of LDL cholesterol by the Friedewald formula may be inaccurate for assessment of cardiovascular risk in patients with type II diabetes and may not be appropriate for management of lipoprotein abnormalities in those diabetic patients.

Decreased endogenous antioxidant enzymatic status in essential hypertension.

Several lines of evidence suggest that patients with essential hypertension have impaired endothelial nitric oxide activity and increased superoxide anion production. However, the mechanisms underlying these abnormalities remain unknown. We measured enzymatic superoxide dismutase (SOD) and glutathione peroxidase (GPX) activities in erythrocytes and whole blood, respectively, in 30 newly-diagnosed, normolipidaemic untreated mild hypertensive patients and in 164 age-matched healthy controls. SOD and GPX activities in hypertensive patients (806 ± 225 U/Hb.g and 5491 ± 2073 U/L, respectively) were significantly lower than in the control group (931 ± 202 U/Hb.g and 6669 ± 1560 U/L, respectively) (P < 0.005). no significant association was found between these antioxidant enzyme activities and blood pressure in normotensive controls. in the hypertensives, only log-transformed sod activity showed a significant negative correlation with systolic and diastolic blood pressure (r = 0.37, P < 0.05; r = 0.64, P < 0.0001, respectively). the low endogenous antioxidant enzyme activities observed may in turn result in decreased superoxide anion removal leading to nitric oxide inactivation.

Lipoprotein profile in men with peripheral vascular disease. Role of intermediate density lipoproteins and apoprotein E phenotypes.

BackgroundThe role of lipoprotein disturbances in the development of peripheral vascular disease (PVD) has not been sufficiently clarified. Methods and ResultsThe relations among concentrations of intermediate density lipoproteins (IDL), apoprotein (apo) B, apo E, and other lipoproteins were studied in 102 men with PVD and 100 healthy men who formed the control group. Patients with PVD had significantly higher levels of serum triglycerides, very low density lipoprotein (VLDL) cholesterol, VLDL triglycerides, VLDL proteins, IDL cholesterol, and IDL triglycerides and lower levels of high density lipoproteins (HDL) than controls. Serum cholesterol and triglycerides were normal in 30 patients (cholesterol, < 5.2 mmol/l; triglycerides, < 2.3 mmol/1), who had significant increases in IDL triglycerides and significant decreases in HDL cholesterol compared with the 47 controls, who had normal cholesterol and triglyceride levels. Patients with more severe distal involvement showed higher cholesterol and triglycerides carried by IDL and a greater reduction in HDL cholesterol. Smoking patients with PVD showed increased VLDL cholesterol and VLDL triglycerides and lower HDL concentrations. Apo E polymorphism in our study population does not differ from that reported for other European populations. Alleles ∈2 and ∈4 had a major impact on serum triglycerides and VLDL lipids in our patients with PVD ConclusionsLipoprotein disturbances are a major risk factor for PVD. IDL abnormalities play an important role in the development and severity of PVD and should also be considered a vascular risk factor in normocholesterolemic and normotriglyceridemic patients.

Autonomic dysfunction in patients with non-alcoholic chronic liver disease

AIMS To assess the presence of autonomic neuropathy in patients with non-alcoholic chronic liver disease and its relationships with the severity of liver damage. METHODS Thirty non-alcoholic patients with chronic liver disease and 26 healthy control subjects were studied. The silicone imprint technique was used to quantify the number of functioning sweat glands in order to assess peripheral sympathetic dysfunction. Heart rate variations in response to deep breathing at 6 per minute (deltaR6), to a Valsalva maneuver, and with orthostatism (RRmax/RRmin) were determined to assess parasympathetic vagal function. RESULTS Mean values for autonomic tests were significantly lower in the group of patients with non-alcoholic chronic liver disease than in the control subjects. The number of activated sweat glands in the foot was abnormal in 19 (63%) patients. Among vagal tests, Valsalva ratio was abnormal in 14 (46%) and deltaR6 in 11 (36%) patients with liver disease. Vagal neuropathy (two or more abnormal heart rate tests) was definite in nine patients (30%). CONCLUSIONS A high prevalence of abnormalities in both sympathetic and parasympathetic function tests, with a poor relationship with liver function parameters, has been found in patients with non-alcoholic chronic liver disease.

Significance of High Density Lipoprotein-Cholesterol in Cardiovascular Risk Prevention

In the approach to lipid-related risk factors for cardiovascular diseases, serum high density lipoprotein-cholesterol (HDL-C) levels bear a particular significance as this lipoprotein is considered to be an antiatherogenic factor mainly, but not only, because of its influence and impact on reverse cholesterol transport. Hence the need and requirement to consider serum HDL-C levels for both primary and secondary prevention of cardiovascular disease. A particularly important aspect is the association of the ‘low HDL syndrome’ with the metabolic syndrome.These factors force us to consider serum HDL-C level as a therapeutic target by itself, or even in association with low density lipoprotein-cholesterol (LDL-C) levels when the latter are increased. This review stresses the aspects connecting serum HDL-C levels and cardiovascular risk, and looks at the populations that should be considered amenable to therapeutic management because of low serum HDL-C levels.We review therapeutic strategies, both pharmacological and nonpharmacological. The aim of this review is to present therapeutic management recommendations for correcting the proportion of cardiovascular risk that is attributable to changes in HDL-C. Serum HDL-C levels of >40 mg/dL must be a therapeutic target in primary and secondary prevention. This goal is particularly important in patients with low serum HDL-C levels and ischemic heart disease (IHD) or its equivalents, even if the therapeutic target for serum LDL-C levels (<100 mg/ dL) has been achieved. The first choice for this clinical condition is fibric acid derivates. The same therapeutic option should be considered in patients without IHD with low serum HDL-C levels and high cardiovascular risk (>20%), hypertriglyceridemia, type 2 diabetes mellitus, or metabolic syndrome.

Pulmonary tuberculosis in HIV-infected patients with normal chest radiographs

SubjectsThree HIV-infected patients with active pulmonary non-disseminated tuberculosis and normal chest radiograph at clinical presentation and during follow-up are reported. Patients had cough and fever but no other specific symptoms. Löwenstein cultures of specimens from bronchoalveolar lavage in two cases and induced sputum in one yielded Mycobacterium tuberculosis. ConclusionsThe diagnosis of tuberculosis in HIV-infected patients depends greatly on clinical suspicion by the physician, because of its atypical presentation. Failure to perform appropriate diagnostic tests in HIV-infected patients who present with suspected pulmonary disease will result in underdiagnosis and undertreatment of tuberculosis.

Apolipoprotein(a) genetic polymorphism and serum lipoprotein(a) concentration in patients with peripheral vascular disease

Serum lipoprotein(a) (Lp(a)) levels were measured in 89 men with peripheral vascular disease (PVD) and 129 (100 male and 29 woman) healthy controls. Apolipoprotein(a) genetic polymorphism was determined by immunoblotting in all subjects. Patients with PVD had significantly higher serum Lp(a) levels than controls. Apolipoprotein(a) phenotype frequencies in patients with PVD did not differ from those of the control group. Both patients and controls with phenotype S2 had higher serum Lp(a) levels than those with phenotype S4. It should be emphasized that serum Lp(a) levels were significantly higher in PVD patients than controls for those with phenotype S2, S3/S4 and S4. Raised serum Lp(a) levels together with other lipoprotein abnormalities in patients with PVD imply a high cardiovascular risk. Genetic polymorphism clearly influences serum Lp(a) levels both in patients and controls. In patients with PVD, environmental and/or other genetic factors must play a role in raising Lp(a) levels.

Anticardiolipin antibodies and acquired immunodeficiency syndrome : prognostic marker or association with HIV infection ?

SummaryAnticardiolipin antibodies (ACA) frequently appear in patients with autoimmune disorders such as systemic lupus erythematosus, and have also been detected in infections, neoplasia, the primary antiphospholipid syndrome, in association with certain medications and also in subjects without apparent disease. Recently, anticardiolipin antibodies have been described in the acquired immunodeficiency syndrome. Eighty-four human immunodeficiency virus (HIV)-infected patients were studied to assess the influence of risk factors for HIV infection and of the stage of HIV-1 infection on the prevalence of IgG-ACA in HIV-seropositive patients. Patients were divided in two groups, one composed of 38 asymptomatic HIV-infected individuals and the other of 46 AIDS patients. A control group of 42 healthy HIV-negative blood donors was also studied. All subjects of the control group were IgG-ACA-negative. Of the 84 HIV-positive patients, 50 were IgG-ACA positive (59.5%) and 34 IgG-ACA negative (40.5%). None of the HIV-positive patients presented any thromboembolic phenomena. No significant differences were found with respect to sex, risk factors and stage of disease when the presence of IgG-ACA in HIV-positive patients was considered. ACA does not appear to be a pronostic marker in HIV-1-infected subjects. The presence of IgG-ACA is probably related to HIV-1-infection itself, and is indicative of impaired humoral immunity in these patients.ZusammenfassungAnticardiolipin-Antikörper (ACA) treten häufig bei Patienten mit Autoimmunkrankheiten wie Lupus erythematodes auf, wurden aber auch im Zusammenhang mit Infektionen, Neoplasien, dem primären Antiphospholipid-Syndrom und bestimmten Medikamenten beobachtet oder bei Personen ohne jegliche erkennbare Erkrankung. Kürzlich wurden Anticardiolipin-Antikörper bei erworbener Immunschwäche beschrieben. Um den Einfluß von Risikofaktoren für eine HIV-Infektion und des Krankheitsstadiums auf die Prävalenz von IgG- ACA zu ermitteln, wurden 84 HIV-infizierte Patienten untersucht. Sie wurden in zwei Gruppen, 38 asymptomatische HIV-Infizierte und 46 AIDS-Patienten unterteilt und mit einer Kontrollgruppe von 42 gesunden, HIV-negativen Blutspendern verglichen. Die Kontrollpersonen waren alle ACA-negativ. Aus der Gesamtgruppe der 84 HIV-positiven Patienten wiesen 50 ACA-IgG auf (59,5%), 34 waren negativ (40,5%). Thromboembolische Phänomene waren bei keinem dieser HIV-positiven Personen zu beobachten. Es bestand keine signifikante Differenz zwischen positiven und negativen ACA-Befunden hinsichtlich Geschlecht der Patienten, Risikofaktoren und Krankheitsstadium der HIV- Infektion. Bei HIV-1-Infizierten scheint der Nachweis von ACA keine prognostische Bedeutung zu haben. Die Antikörper sind wahrscheinlich mit der HIV-Infektion selbst assoziiert und ein Zeichen für die gestörten humoralen Immunfunktionen dieser Patienten.