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Biomedical subjects

U De Faire

Publications and source records attributed to U De Faire.

At least 19 recordsLinked to original sources

Higher relative, but lower absolute risks of myocardial infarction in women than in men: analysis of some major risk factors in the SHEEP study. The SHEEP Study Group.

OBJECTIVES: Middle-aged men have often been the subjects of multifactorial studies of myocardial infarction (MI) risk factors. One major objective of the SHEEP study was to compare the effects of different MI risk factors in women and men. DESIGN: SHEEP (Stockholm Heart Epidemiology Program) is a population-based case-referent study of causes of MI (first event) in Swedish women and men aged 45-70 years. During the period 1992-94, 2246 cases of MI were identified; 34% of the cases were women and 27% of the cases were fatal. One referent per case was chosen randomly from the Stockholm County population after stratification for the case's sex and age. Logistic regression was used to estimate the relative risks associated with risk factors of primary interest (diabetes, hypercholesterolaemia, hypertriglyceridaemia, hypertension, overweight, physical inactivity, smoking and job strain). RESULTS: The relative risk estimates ranged from 1.5 to 4.4 in women and from 1.3 to 2.9 in men (results for nonfatal cases and their referents). None of the 95% confidence intervals included 1.0. The relative risks were higher in the women than in the men (101-180%). The absolute risks, however, were all lower in the women than in the men. Estimates of Rothman's synergy index for gender ranged from 1.0 (hypertension) to 1.8 (current smoking). CONCLUSIONS: The indications of some effect modification due to sex (stronger risks in men for certain exposures) invoke the question of possible mechanisms.

Aged↗

A genetic polymorphism in connexin 37 as a prognostic marker for atherosclerotic plaque development.

BACKGROUND AND OBJECTIVES: Atherosclerosis is a multifactorial disease, in part characterized by chronic inflammatory changes in the vessel wall and loss of normal physical and biochemical interactions between endothelial cells and smooth muscle cells. Previous studies [Hu J., Cotgreave IA. J Clin Invest; 99: 1-5] have provided molecular links between inflammation and myoendothelial communication via gap junctions, suggesting that these structures may be important in the development of the atherosclerotic vessel phenotype. In order to strengthen this premise, the aim of the present work was to probe for structural polymorphisms in connexin 37, a gap junctional protein uniquely expressed in endothelial cells, and to assess for potential genotypic segregation in individuals displaying atherosclerotic plaque. METHODS AND RESULTS: Computer-based comparisons of Expressed Sequence Tags (ESTs) predicted a polymorphism in the human gap junctional protein connexin 37 (cx37). The C1019-T mutation results in a proline to serine shift at codon 319 (cx37*1-cx37*2). A Restriction Fragment Length Polymorphism (RFLP) assay, involving the insertion of a novel Drd I cleavage site in the proline variant revealed a statistically significant over-representation of the cx37*1 allele in association with atherosclerotic plaque-bearing individuals (Odds-ratio for the homozygote = 2.38, Chi2 = 7.693, P = 0.006), in comparison to individuals lacking plaque, irrespective of a history of hypertension. CONCLUSIONS: These data suggest that the C1019-T polymorphism in cx37 may provide 'single gene marker', which could be useful in assessing atherosclerotic plaque development, particularly in cardiovascular risk groups such as those with borderline hypertension.

Adult↗

Antibodies to platelet-activating factor are associated with borderline hypertension, early atherosclerosis and the metabolic syndrome.

OBJECTIVE: Platelet-activating factor (PAF) is a phospholipid inflammatory mediator which is synthesized by a variety of cells, including monocytes and endothelial cells, and PAF can be retained in activated endothelial cell membranes. Furthermore, PAF-like lipids are produced in other phospholipid membranes as in oxidized LDL. Atherosclerosis is a chronic inflammation in the artery wall, but little is known about the role of immune reactions in the early stages of development of cardiovascular disease. In the present study we investigated if there are antibodies to PAF (aPAF) that may play a role in borderline hypertension and early atherosclerosis. DESIGN: Seventy-three men with borderline hypertension (BHT) and 73 age-matched normotensive (NT) men (diastolic blood pressure 85-94 and <80 mmHg, respectively) were recruited from a population screening programme. Antibody levels were determined by use of ELISA. Carotid intima-media (IM)-thickness and atherosclerosis was determined by B-mode ultrasonography. RESULTS: BHT men had 49.3% higher aPAF levels of IgG class than NT controls (P = 0.0007). Antibodies to the biologically inactive lysoPAF did not differ between BHT and NT group. aPAF levels were associated with IM-thickness in the left (P = 0.02) and right (P = 0.009) carotid artery. Furthermore, aPAF levels were enhanced in individuals with the metabolic syndrome (n = 44) as compared to those without (n = 102; P = 0.009), and also significantly associated with insulin levels (P = 0.02) and insulin resistance (P = 0.02). CONCLUSIONS: aPAF antibodies may reflect early vascular changes and thus serve as novel markers for disease, and they may also be pathogenic, by eliciting an inflammatory reaction in the vascular wall.

Adult↗

Helicobacter pylori seropositivity is not associated with inflammatory parameters, lipid concentrations and degree of coronary artery disease.

OBJECTIVES: To determine the prevalence of chronic infection with Helicobacter pylori (HP) in patients with established coronary artery disease (CAD) and in healthy controls. Furthermore, to investigate whether HP infection is associated with inflammatory parameters, lipid concentrations and degree and progression of CAD. DESIGN: A case-control study combined with a prospective angiographic study. SETTING: Stockholm Metropolitan Area, Sweden. PATIENTS AND METHODS: A material consisting of 92 young men aged 40.9 +/- 3.2 (mean +/- SD) years, with previous myocardial infarction and documented coronary atherosclerosis, and 95 healthy sex-matched controls, aged 43.2 +/- 3.0 (mean +/- SD) years, with similar socio-economic status and ethnic background was analysed for the prevalence of HP seropositivity, plasma concentrations of the inflammatory parameters fibrinogen, tumour necrosis factor alpha and orosomucoid, and serum concentrations of lipids. The impact of HP seropositivity on degree and progression of CAD, as assessed by quantitative coronary angiography, was also determined. RESULTS: The study population of mainly Scandinavian origin had a low prevalence of HP seropositivity in comparison with previously published European populations. No significant increase in HP seropositivity was found in patients compared with controls (42.2 vs. 32.6%). Furthermore, HP infection was not associated with increased levels of inflammatory parameters, lipid concentrations or with degree of angiographically determined CAD at baseline, or progression of CAD and clinical events over 5 years. CONCLUSIONS: HP infection is not associated with inflammatory parameters and lipid concentrations and could not be confirmed as a risk factor for CAD.

Adult↗

Long-term use of smokeless tobacco and physical performance in middle-aged men.

To determine the influence of prolonged nicotine exposure on maximal physical working capacity, a study of clinical measures of physical fitness and cardiovascular response to exercise was performed in 144 healthy men, 35-60 years old, subdivided into smokeless tobacco users, smokers and non-users of tobacco. Regular users of smokeless tobacco, with exposures of more than 20 years, showed similar maximal oxygen uptake (mean 3.48 L min-1, SD 0.49, n = 48) to non-users (mean 3.51 L min-1, SD 0.51, n = 65). In smokeless tobacco users, higher blood pressure and heart rate values were observed at rest and at submaximal work, after exposure to tobacco shortly before the exercise test, but not at maximal work. However, significantly lower maximal oxygen uptake was found for smokers (mean 2.88 L min-1, SD 0.49, n = 31) compared with non-users (P < 0.001). Plasma concentration of continine, the main metabolite of nicotine, was significantly higher in smokeless tobacco users (mean 347 ng mL-1, SD 175, n = 48) than in smokers (mean 253 ng mL-1, SD 153, n = 31, P < 0.001). The findings indicate that long-term use of smokeless tobacco does not significantly influence exercise capacity in healthy, physically well-trained subjects.

Adult↗

Elevation of plasminogen activator inhibitor 1 in borderline hypertension is linked to concomitant metabolic disturbances.

In the present study we investigated plasma levels of plasminogen activator inhibitor 1 (PAI-1), fibrinogen and von Willebrand factor (vWF) in borderline hypertensive (BHT) men [diastolic blood pressure (DBP) 85-94 mmHg, n = 75] and age-matched normotensive (NT) control subjects (DBP < or = 80 mmHg, n = 75), in relation to smoking, body mass index (BMI) and fasting lipoprotein and insulin levels. PAI-1 levels were elevated in the BHT group [16.3 vs. 13.7 arbitrary units (AU), P = 0.032], whereas levels of fibrinogen and vWF were similar in the two groups. The PAI-1 elevation was even more pronounced in dyslipidaemic BHT subjects than in normolipidaemic NT subjects (20.0 vs. 10.3 arbitrary units (AU), P = 0.001). PAI-1 levels showed strong correlations with insulin, lipoproteins and BMI (P < 0.01-0.001), but not with DBP. The results show that disturbances in the fibrinolytic system appear even in borderline hypertension. The elevation of PAI-1 levels seems to be more strongly linked to concomitant metabolic disturbances than to blood pressure levels.

Biomarkers↗

The Swedish Trial in old patients with hypertension-2 (STOP-hypertension-2): a progress report.

OBJECTIVE: The Swedish Trial in Old Patients with Hypertension-2 (STOP-Hypertension-2) was designed by a project group of the Swedish Hypertension Society to test whether the "newer" treatment alternatives (ACE inhibitors and calcium antagonists) are as good as, better or less good than, the "older" ones (beta-blockers and diuretics) in terms of preventing cardiovascular morbidity and mortality in elderly hypertensives. The aim of the present paper is to report on the progress of the study. DESIGN: Prospective, open trial with blinded end-point committee and centralized randomization (PROBE design). STOP-Hypertension-2 may be regarded as a scientific follow-up of the previously published Swedish Trial in Old Patients with Hypertension (STOP-Hypertensioon-1) (6) using the same study organization. SUBJECTS: By the end of 1994 when recruitment was stopped, 6628 hypertensive men (34%) and women (66%) aged 70-84 (mean age 76) had been included at 312 Swedish health centres (out of approximately 850). In the whole cohort 11% are diabetics and 9% smokers. The mean total cholesterol value is 6.5 mmol/L. RESULTS: In the whole study cohort, blood pressure was lowered from 194/98 mmHg to 167/85 mmHg after one year. At the end of 1995, 319 fatal events (all-cause mortality) had been reported, corresponding to a mortality rate of 21.3 per 1000 person-years. CONCLUSION: In STOP-Hypertension-2, 6628 elderly hypertensive have been randomized to three different treatment regimes: beta-blocker+diuretics (the active treatment arm in STOP-Hypertension-1), ACE inhibitors, or calcium antagonists. Their average lowering of blood pressure was 27/13 mmHg and end-points have occurred at the expected rate. Thus, it should be possible to terminate STOP-Hypertension-2 within two to three years.

Aged↗

Impaired glucose and insulin metabolism in borderline hypertension.

This study investigated glucose and insulin metabolism in borderline hypertension (BHT) defined as repeated diastolic blood pressures (DBP) of 85-94 mmHg. Seventy-five BHT and 75 age-matched normotensive (NT, DBP < or = 80 mmHg) men were recruited from a population screening programme. Plasma lipoproteins were determined and an oral glucose tolerance test was performed (WHO criteria). Fasting insulin was significantly higher in the BHT group (17.2 vs 14.2 mU/ml, p < 0.001), whereas fasting blood glucose levels were similar in the two groups, indicating a reduced insulin sensitivity. The BHT group had significantly lower levels of HDL cholesterol and higher levels of plasma triglycerides, VLDL cholesterol and VLDL triglycerides. When adjusted for BMI these differences disappeared, whereas the basal insulin levels remained significantly elevated (F = 10.7, p < 0.001). These results indicate that an altered glucose and insulin metabolism is present already in the early stages of hypertension. They also suggest that these disturbances are only partly dependent on BMI. This supports the hypothesis that reduced insulin sensitivity could be of importance in the early phases of essential hypertension.

Adult↗

Coronary angiographic changes during 2 years after myocardial infarction largely undetected by repeated tomographic thallium-201 scintigraphy and not reflected by clinical symptoms.

Repeated coronary angiographies and single photon emission computed tomographies (SPECT) were performed at 9 and 33 months after myocardial infarction (MI) in 47 young men. Coronary lesions were classified in eight grades with respect to the reduction of the luminal diameter. The progression and regression of two steps or more in lesions of grade 2 or more, the recanalization of coronary thrombosis and an increase in collaterals were recorded. Patients were divided into three groups with regard to (A) deterioration, (B) improvement and (C) no changes in the three major coronary regions, respectively. Overall, 23 patients (49%) showed changes between the first and the second investigation. A simplified method using summarized short-axis slices for evaluation of the thallium-201 SPECT showed a significant difference in change of regional myocardial uptake of thallium-201 between groups A and B (P = 0.047) but not between the groups A and C, in lateral myocardial regions. No significant differences were found between any of the groups in respect of the anterior or inferior myocardial regions. These findings were not explained by changes in clinical status, maximum heart rate or workload, or by changes in medication. Our results suggest that substantial changes in coronary morphology can take place during the 2 years following MI without consistent changes in clinical symptoms or regional myocardial perfusion.

Adult↗

Plasma growth factor activity and cardiac wall thickness.

OBJECTIVES: The aim of this study was to investigate the growth factor activity in plasma (GFAP) in hypertension, and the correlation of GFAP to blood pressure levels, cardiac structural changes and platelet activation at rest and during exercise. SUBJECTS: Fifteen untreated hypertensive subjects and 15 normotensive controls were recruited from a blood pressure screening programme. INTERVENTIONS: GFAP before and after 30 min of strenuous exercise was analysed as the ability of patient or control plasma to stimulate incorporation of 3H-thymidine in cultured human smooth muscle cells. M-mode echocardiography was performed and platelet activity was measured by the excretion of the urinary metabolite of thromboxane A2. RESULTS: There were no significant differences in GFAP or platelet activation at rest or after exercise between the groups. The fractions of labelled cells were 52.6% vs. 56.6% (HT vs. NT) at rest. Septum and posterior wall end-diastolic thicknesses (PWT[D]) were significantly increased in the HT group (10.4 +/- 0.3 vs. 9.2 +/- 0.3 mm and 11.4 +/- 0.5 vs. 10.0 +/- 0.4 mm, respectively, P < 0.05). PWT(D) was significantly correlated to GFAP (r = 0.40, P = 0.04) and to blood pressure (r = 0.53, P < 0.005) but there was no correlation between blood pressure and GFAP. CONCLUSION: The data suggest that GFAP could play a role in the early development of cardiac hypertrophy in hypertension, but that this effect does not seem to be directly linked to blood pressure levels alone.

Adult↗

Association between high levels of growth factors in plasma and progression of coronary atherosclerosis.

Although intimal proliferation of smooth muscle cells (SMC) is recognized as one of the key mechanisms in the development of atherosclerosis, our knowledge of the role of circulating growth factors for SMC in this process is limited. In the present study the plasma levels of platelet-derived growth factor (PDGF), beta-thromboglobulin (beta-TG), platelet factor 4 (PF 4) and total growth factor activity were determined in a group of 30 young postinfarction patients who had participated in an angiographic study of mechanisms associated with progression of coronary atherosclerosis. Significant correlations were found between the total growth factor activity in plasma and progression (r = 0.42, P < 0.05), as well as severity (r = 0.52, P < 0.01), of global coronary atherosclerosis. Attempts to identify the nature of the total growth factor activity indicated that less than 20% could be attributed to PDGF, the major serum mitogen for SMC. PDGF levels determined by radioimmunoassay were not related to progression or severity of global coronary atherosclerosis, but showed a significant association with the number and severity of distinct stenoses (r = 0.40, P < 0.05). Due to the retrospective design of this study, it is not possible to conclude whether there is a causal relationship between circulating growth factors and development of coronary atherosclerosis.

Adult↗

Serum lipoproteins and apolipoproteins in young male survivors of myocardial infarction.

Concentrations of serum lipoprotein lipids and apolipoproteins A-I, A-II and B were determined 3-6 months after myocardial infarction in 116 males below the age of 45 and in 116 age-matched controls. Among single variables the sum of cholesterol concentration in VLDL and LDL divided by the HDL cholesterol level was the best discriminator between patients and controls. The concentrations of serum triglycerides, apolipoprotein B, VLDL triglycerides and cholesterol, serum cholesterol, HDL cholesterol and LDL triglycerides, in that order, were better discriminators than was LDL cholesterol level. Among variables reflecting HDL concentration and composition HDL cholesterol was the best discriminator followed by HDL2 cholesterol, apolipoprotein A-I and the HDL cholesterol/apolipoprotein A-I ratio. Multivariate analysis indicated independent significance of elevated VLDL lipid and LDL cholesterol concentrations, and a decreased HDL cholesterol concentration, in relation to MI. The present data suggest that a disturbed triglyceride metabolism, in addition to elevated LDL and decreased HDL cholesterol levels, has an independent and pathogenetic significance for MI at a young age.

Adult↗

Immunologic evaluation of patients with ischemic heart disease. Genetic determination and relation to disease.

Delayed skin hypersensitivity and serum immunoglobulins were studied in relation to the severity of ischemic heart disease in 18 male monozygotic and 13 male dizygotic twin pairs, aged 55-78 years. The twin pairs were selected from the Swedish Twin Registry. Low IgG was seen in patients with myocardial infarction and definitive angina pectoris. No correlation between skin anergy and the severity of ischemic heart disease was found. These findings may support the possibility that immunological mechanisms play a part in the pathogenesis of ischemic heart disease. Significant F-ratios for IgA and differential white cell count support a genetic determination of these variables.

Aged↗