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Biomedical subjects

J M Mostaza

Publications and source records attributed to J M Mostaza.

At least 19 recordsLinked to original sources
PubMed2002

Effect of apoE genotype on the hypolipidaemic response to pravastatin in an outpatient setting.

BACKGROUND: Considerable variability exists in the plasma lipid and lipoprotein response to statin treatment due, in part, to genetic factors. The gene for apolipoprotein E (ApoE) is polymorphic and the different genotypes modulate baseline lipid levels. The objective of the present study was to evaluate the effect of the apoE genotype on the lipoprotein response to pravastatin treatment in an outpatient population followed-up in several different clinics across Spain. Subjects and methods. Subjects (n=401; 56% female; mean age 57 years), who were hypercholesterolaemic despite a diet poor in saturated fat and cholesterol, were treated according to NCEP-ATP II guidelines. Plasma lipids and lipoproteins were measured centrally before and after 16 weeks of treatment with 20 mg day-1 of pravastatin. RESULTS: ApoE genotype distributions were 3.2% with varepsilon2/3, 73.1% with varepsilon3/3 and 22.4% with varepsilon3/4 or varepsilon4/4. ApoE genotype did not have any effect on baseline lipid levels except on triglycerides such that the carriers of the varepsilon2 allele had concentrations significantly greater than those subjects with varepsilon3/3 genotype and carriers of the varepsilon4 allele after adjustment for age, gender and body mass index (BMI) (P < 0.001). Once adjusted for age, gender, BMI and baseline lipid levels, the apoE polymorphism did not significantly influence the plasma lipid and lipoprotein response to pravastatin. CONCLUSION: ApoE genotype appears not to influence the hypolipidaemic effect of pravastatin in patients monitored in a general outpatient setting.

Ambulatory Care↗
PubMed2001

[Apolipoprotein E polymorphism and coronary disease].

BACKGROUND: Apolipoprotein E (Apo E) plays an important role in atherogenesis. Apo E is polymorphic with three codominant alleles: *2, *3 and *4. Inthis study we evaluated the association between *4 allele and coronary heart disease in hypercholesterolemic subjects from Spain. SUBJECTS AND METHOD: We selected 389 subjects (56% women, mean age 57 years) with hypercholesterolemia who had been on a 6-weeks low fat, low cholesterol diet. Measurement of lipid and lipoprotein concentrations and determination of apoE genotype were carried out in a centralized laboratory. RESULTS: ApoE distribution was as follows: *2/*33%, *3/*3 75%, *3/*4 20%, *4/*4 1% and *2/*41%. Subjects were grouped into *4 (n = 83) or no *4 (n = 303) according to the presence or absence of the *4 allele. Three *2/*4 cases were excluded. Prevalence of coronary artery disease was 15.7% in *4 and 6.9% in no *4 (OR 2.49, 95% CI 1.19-5.22). The relationship persisted significant after correction for age, sex, cardiovascular risk factors and serum concentrations of total cholesterol, HDL-cholesterol and triglycerides by multiple logistic regression analysis (OR2.56, 95% CI 1.03-6.39).Conclusión:In Spain, *4 carriers have a higher prevalence of coronary artery disease than no analysis *4 carriers.

Apolipoproteins E↗
PubMed2001

Pravastatin therapy increases procollagen I N-terminal propeptide (PINP), a marker of bone formation in post-menopausal women.

BACKGROUND: The aim of our study was to evaluate whether pravastatin treatment affected biochemical markers of bone turnover. METHODS: Thirty-six hypercholesterolemic post-menopausal women, not on hormonal replacement therapy, were selected from a population study evaluating factors affecting cholesterol response to pravastatin. After a 6-week period on a 30% fat diet, participants received treatment with 20 mg/day of pravastatin during a 16-week follow-up period. Pre- and post-treatment samples were analyzed for procollagen I aminoterminal peptide (PINP) and bone alkaline phosphatase (bAP) as markers of bone formation, carboxyterminal telopeptide of collagen I (CTX) as a marker of bone resorption, and procollagen III aminoterminal propeptide (PIIINP) as a marker of fibrogenesis. RESULTS: Total cholesterol decreased from 7.26+/-0.83 to 6.1+/-0.77 mmol/l with pravastatin treatment. PINP levels significantly increased (from 33.6+/-13 to 37.4+/-16, p=0.03) without changes in bAP or CTX. Individual changes in PINP correlated with individual reduction in cholesterol levels (r=0.337, p=0.04). There was no significant change in PIIINP concentration. CONCLUSIONS: Pravastatin treatment increased PINP levels, a marker of bone formation, in hypercholesterolemic, post-menopausal women, without affecting bone resorption. PIIINP concentration, a marker of liver fibrogenesis, was not affected by the treatment.

Adult↗
PubMed2000

Cholesterol reduction improves myocardial perfusion abnormalities in patients with coronary artery disease and average cholesterol levels.

OBJECTIVES: We sought to evaluate whether pravastatin treatment increases myocardial perfusion, as assessed by thallium-201 single-photon emission computed tomographic (SPECT) dipyridamole testing, in patients with coronary artery disease (CAD) and average cholesterol levels. BACKGROUND: Previous studies in hypercholesterolemic patients have demonstrated that cholesterol reduction restores peripheral and coronary endothelium-dependent vasodilation and increases myocardial perfusion. METHODS: This was a randomized, placebo-controlled study with a cross-over design. Twenty patients with CAD were randomly assigned to receive 20 mg of pravastatin or placebo for 16 weeks and then were crossed over to the opposite medication for a further 16 weeks. Lipid and lipoprotein analysis and dipyridamole thallium-201 SPECT were performed at the end of each period. The SPECT images were visually analyzed in eight myocardial segments using a 4-point scoring system by two independent observers. A summed stress score and a summed rest score were obtained for each patient. Quantitative evaluation was performed by the Cedars-Sinai method. The magnitude of the defect was expressed as a percentage of global myocardial perfusion. RESULTS: Total and low density lipoprotein cholesterol levels during placebo were 214 +/- 29 mg/dl and 148 +/- 25 mg/dl, respectively. These levels with pravastatin were 170 +/- 23 mg/dl and 103 +/- 23 mg/dl, respectively. The summed stress score and summed rest score were lower with pravastatin than with placebo (7.2 +/- 2.3 vs. 5.9 +/- 2.3, p = 0.012 and 3.2 +/- 1.6 vs. 2.4 +/- 2.2, p = 0.043, respectively). Quantitative analysis showed a smaller perfusion defect with pravastatin (29.2%) as compared with placebo (33.8%) (p = 0.021) during dipyridamole stress. No differences were found at rest. CONCLUSIONS: Reducing cholesterol levels with pravastatin in patients with CAD improves myocardial perfusion during dipyridamole stress thallium-201 SPECT.

Aged↗
PubMed1998

Abnormal metabolism of free fatty acids in hypertriglyceridaemic men: apparent insulin resistance of adipose tissue.

OBJECTIVE: There is growing evidence that endogenous hypertriglyceridaemia is frequently accompanied by a state of insulin resistance. The present study was performed to determine whether patients with primary endogenous hypertriglyceridaemia commonly have abnormalities in plasma concentrations and turnover rates of free fatty acids (FFA), which could reflect a state of insulin resistance in adipose tissue and could account for raised plasma triglycerides. DESIGN: Hypertriglyceridaemic and normotriglyceridemic control patients underwent measurements of plasma concentrations and turnover rates of FFA. Fat weights in both groups were determined by hydrodensitometry, and fat distribution was assessed by skin-folds and measurement of waist and hip circumferences. Other measurements included plasma glucose, insulin, lipids, and lipoproteins. SUBJECTS: Fifteen men with normal plasma triglycerides and 21 men with primary endogenous hypertriglyceridaemia were studied. Men in both groups varied in body weights and total fat weights, but total fat weights were entirely overlapping for the two groups. Waist-to-hip ratios and waist circumferences also were similar for the two groups. RESULTS: For any total body fat content or waist circumference, most hypertriglyceridaemia patients had higher mean plasma concentrations of FFA and higher turnover rates (flux) for FFA than did normotriglyceridemic patients. Hypertriglyceridaemic patients also had higher fasting insulin concentrations for a given body fat content. In general, both FFA flux and plasma insulin levels were positively correlated with plasma concentrations of triglyceride and inversely with high density lipoprotein (HDL) cholesterol. CONCLUSIONS: These studies indicate that many patients with primary endogenous hypertriglyceridaemia have increased flux of FFA and hyperinsulinemia that cannot be explained either by increased total body fat content or by greater waist circumferences than observed in normotriglyceridemic patients.

Adipose Tissue↗
PubMed1998

[Endothelial dysfunction and metabolic syndrome].

Endothelial dysfunction and insulin resistance coexist in a significant proportion of subjects. Both are associated with a great number of cardiovascular risk factors which probably explains their relation. Although there are direct mechanisms that physiopathologically may relate both disorders, the practical significance of an independent and direct connection is uncertain.

Cardiovascular Diseases↗
PubMed1996

Effectiveness of low-dose crystalline nicotinic acid in men with low high-density lipoprotein cholesterol levels.

BACKGROUND: Hypoalphalipoproteinemia (low serum concentration of high-density lipoprotein cholesterol [HDL-C]) is a common pattern of dyslipidemia associated with coronary heart disease. High doses of nicotinic acid effectively raise HDL-C levels in this condition, but they are commonly accompanied by side effects. The efficacy of low doses of nicotinic acid that may produce fewer side effects has not been adequately studied. OBJECTIVE: To determine the effects of low-dose nicotinic acid on HDL-C levels in patients with hypoalphalipoproteinemia. METHODS: Forty-four men with low HDL-C levels (< 1.03 mmol/L [< 40 mg/dL]) entered the study. Twenty-four patients otherwise had normal lipid levels, and 20 were moderately hypertriglyceridemic (range of plasma triglyceride levels, 2.82 to 5.64 mmol/L 250 to 500 mg/dL). The trial consisted of 3 phases; each phase lasted 8 weeks. The first phase was diet only (30% fat diet); in the second phase, crystalline nicotinic acid was added at 1.5 g/d; and in the third phase, the dose was increased to 3 g/d. RESULTS: Of the 44 patients who entered the study, 37 completed the low-dose phase (1.5 g/d); the remaining patients were withdrawn because of side effects to nicotinic acid. Four other patients who completed the low-dose phase were excluded from the higher dose phase because of side effects that developed when they were receiving the low dose. Ten other patients withdrew during the high-dose phase because of side effects. In both groups, responses to nicotinic acid therapy tended to be dose-dependent. For both groups, the higher dose generally produced a greater reduction in apolipoprotein B-containing lipoproteins and a greater rise in HDL-C levels. However, for both groups, the low dose of nicotinic acid gave an average 20% increase in HDL-C levels. CONCLUSIONS: A low dose (1.5 g/d) of crystalline nicotinic acid causes an average 20% increase in HDL-C levels and significantly lowers triglyceride levels in both normolipidemic and hyperlipidemic patients with low HDL-C levels. Although the changes induced by this dose are less than those that can be achieved by a higher dose, the lower dose is better tolerated. Nicotinic acid may be useful in combined drug therapy for secondary prevention of coronary heart disease, and if higher doses cannot be tolerated, use of a lower dose should still be useful for producing a moderate rise in HDL-C levels in patients with hypoalphalipoproteinemia.

Crystallization↗
PubMed1996

[Urate production in a porcine model of myocardial ischemia-reperfusion].

OBJECTIVE: This study was designed to investigate urate production by swine hearts using an in vivo regionally ischemic-reperfused model. ANIMALS AND METHODS: Ten female pigs underwent 60 minutes of myocardial ischemia by clamping of the left anterior descending artery and afterwards 120 minutes of reperfusion. Epicardial biopsies and blood samples from coronary sinus were taken before ligation, at the end of ischemic period and 5, 30, 60 and 120 minutes upon reperfusion. RESULTS: During ischemia, tissue levels of ATP and ADP greatly declined with a subsequent increase in the concentration of AMP, inosine and hypoxanthine (33 +/- 12 vs 93 +/- 17, 26 +/- 8 vs 768 +/- 86 and 32 +/- 10 vs 219 +/- 26 nmol/g dry weight, p < 0.01 for each). Despite the great increase in the hypoxanthine levels, uric acid concentration remained constant (69 +/- 9 vs 32 +/- 12 nmol/g dry weight, NS). Hypoxanthine, xanthine and uric acid concentrations increased in blood samples obtained from the coronary sinus at the end of ischemic period (17.99 vs 31.03 nmol/ml, p < 0.01, 0.29 vs 1.45 nmol/ml, p < 0.05 and 1.20 vs 2.31 nmol/ml, p < 0.01 respectively) and were enhanced upon reperfusion (35.8 and 3.89 nmol/ml for hypoxanthine and uric acid respectively, p < 0.05) without any significant modifications in their concentrations at the arterial level. CONCLUSION: These results demonstrate that the ischemic-reperfused swine heart produces urate probably outside the myocardium.

Animals↗
PubMed1996

[Increase of myocardial perfusion during antilipemic treatment in patients with ischemic cardiopathy].

OBJECTIVES: To evaluate if cholesterol lowering therapy with simvastatin increases myocardial perfusion, assessed by Thallium-201 single photon emission computed tomography (SPECT) after dipyridamole, in patients with coronary artery disease. PATIENTS AND METHODS: Ten hypercholesterolemic subjects with coronary artery disease were selected for a pilot study. Lipid and lipoprotein analysis and Thallium-201 SPECT were performed before and after 16 weeks of treatment with 40 mg of simvastatin QD. SPECT images were qualitatively analyzed in 8 myocardial segments using a 4 point scoring system. Quantitative evaluation was performed in 13 segments. The myocardial region with the maximal mean counts per pixel on the stress study was considered the reference region. TI201 activity in all other myocardial regions was expressed as a percentage of the activity in the reference region. RESULTS: Total cholesterol and LDL cholesterol were reduced by 28.4% and 37.1% with treatment. Global myocardial perfusion was increased in all patients. Qualitative analysis demonstrated that cholesterol lowering improved myocardial perfusion during dipyridamole stress. Quantitative analysis showed an increased global perfusion during stress (41.8% vs 54.6%; p < 0.0001), due to increased perfusion of previous ischemic segments (32.4% vs 49.4%; p < 0.0001) but without changes in previous normally perfused segments (71.5% vs 71.3%). CONCLUSION: Reduction of cholesterol levels in hypercholesterolemic subjects with coronary artery disease increases myocardial perfusion in ischemic segments during dipyridamole stress test as assessed by single photon emission computed tomography (SPECT).

Adult↗
PubMed1992

[Regression of coronary arteriosclerosis with hypolipidemic treatment, myth or reality?].

Coronary atherosclerosis regression with hypolipemiant treatment is a well known fact in the animal model since years ago. In humans, during these last years, several clinical trials have been performed to ellucidate the truth to this fact. All of these clinical trials have in common the evolutive study of the coronary lesions with angiographies, in patients following treatment with diet, surgery or drugs, to reduce plasmatic cholesterol. Clinical, analytical and angiographic results of said studies are reviewed. We conclude that the bigger the lowering in plasmatic cholesterol levels, smaller is the progression of these coronary lesions and more probable is finding patients with partial regression of the lesions.

Clinical Trials as Topic↗
PubMed1992

[Peritoneal tuberculosis. The characteristics of a not infrequent tuberculosis site].

Laparoscopic, clinical and biological features of 51 patients admitted over a period of 22 years in two university hospitals of Madrid are analyzed. Mean age was 43 years, 30 patients were diagnosed in the period from 1967 to 1978 and in 32 of them, there was predisposing pathology. Main symptoms were abdominal pain, fever, general syndrome and ascites. Ascitic fluid was an exudate in 97% of cases, finding BAAR in one case, being the culture positive in four cases. Diagnostic was made through laparoscopy in 42 cases and using laparotomy in 9 cases, being confirmed with histological procedures in 38 cases and with microbiological procedures in 11 cases. Peritoneal tuberculosis is a non unfrequent tuberculosis localization. Laparoscopy is the more cost-effective diagnostic method of peritoneal tuberculosis.

Age Factors↗
PubMed1991

[AIDS: clinical and necropsy correlation. Analysis of 45 patients].

We have reviewed the autopsies performed on 45 AIDS patients who died in our hospital until June 1989, comparing the post-mortem diagnosis with those made while the patient was alive and in his last hospital admission. Bacterial pneumonia, CMV infection and atypical mycobacteria were the diseases most frequently unnoticed. On the contrary, HIV encephalitis and pulmonary mycosis were the disease with the greatest number of non confirmed clinical diagnosis. The routine performance of necropsy studies to AIDS patients permits to know the most prevalent infections in our environment and should improve the diagnostic precision.

Acquired Immunodeficiency Syndrome↗