ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundMechanisms underlying the previously reported association between a deletion polymorphism in the gene encoding for angiotensin-converting enzyme (ACE) and the risk of myocardial infarction in low-risk subjects are unclear. The purpose of this case-control study was to examine the relation of plasma ACE activity to intimal-medial thickness of the carotid wall measured ultrasonographically in an apparently healthy population.Methods and ResultsWe determined plasma ACE activity 80 pairs of subjects without any history of ischemic heart disease or any treatment of hypertension and diabetes. Cases and control subjects were defined on the basis of intimalmedial thickness measured in the common carotid arteries by mode ultrasound and were matched for sex, sonographer, and the presence of atheromatous plaques. Subjects were selected from a sample of 434 men and 602 women between 60 and 69 years old participating in an ongoing study on vascular aging (EVA). Subjects with intimal-medial thickening (cases) showed a slight but not significant increase in plasma ACE activity in comparison with control subjects (P< .16). However, after exclusion of subjects receiving lipid-lowering drugs, the mean plasma ACE activity became significantly higher in cases than in control subjects (29.9±7.7 U/L versus 27.5±8.0 U/L;n= 54 pairs,P< .03). The mean case-control difference in plasma ACE activity was further increased when analysis was restricted to pairs without carotid atheromatous plaques (n=42 pairs). After adjustment for body mass index, smoking, and systolic blood pressure, the odds ratio for having carotid wall thickening based on 1 SD difference in log ACE was 2.29 (95% confidence interval, 1.16 to 4.52;P< .02).ConclusionsThe results of the study suggest that chronic exposure to high levels of plasma ACE could be involved in structural changes of the arterial wall.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundVesnarinone, a quinolinone derivative, is a recently synthesized positive inotropic agent that has been shown to dramatically improve the survival of patients with heart failure. However, the mechanism of action of vesnarinone remains unknown. Reversible neutropenia complicated with vesnarinone therapy suggests that vesnarinone may modulate the production of cytokines. Because tumor necrosis factor (TNF)-α and other cytokines have been shown to depress myocardial contractility, we investigated the effects of vesnarinone on the production of various cytokines.Methods and ResultsWe studied the effects of vesnarinone on cytokine production by lipopolysaccharide (LPS)-stimulated whole blood from seven patients with heart failure and from five healthy volunteers. Heparinized blood was diluted in RPMI and stimulated with LPS. Vesnarinone was added in a range of 1 to 30 μg/mL, the blood was incubated for 24 hours, and interleukin (IL)-1α, IL-1β, IL-6, TNF-α, interferon (IFN)-γ, and granulocyte colony-stimulating factor (G-CSF) were measured by an enzyme-linked immunosorbent assay. LPS stimulation induced a more prominent increase in TNF-α in patients with heart failure than in healthy volunteers. Vesnarinone inhibited the production of TNF-α and IFN-γ both in healthy volunteers and in patients with heart failure. IL-la and IL-1β were also suppressed in healthy volunteers, but this response was variable, and a significant reduction was not seen in patients with heart failure. Marked inhibition of G-CSF and other cytokines by vesnarinone was observed in one patient who had developed neutropenia as a result of vesnarinone therapy.ConclusionsAlthough the number of study patients was small and the results are preliminary, these findings provide evidence that vesnarinone plays an important role in the regulation of cytokines and suggest that the reduction of cytokine release may contribute to the beneficial effects of the drug in the treatment of heart failure. Furthermore, the measurement of cytokines may be useful in predicting the occurrence of neutropenia, which has been occasionally reported in patients treated with vesnarinone.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Background3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors are widely prescribed for hyperlipidemia, yet their effect on the evolution of coronary atherosclerosis has not been defined.Methods and ResultsTo address this issue, 331 patients with diffuse but not necessarily severe coronary atherosclerosis documented on a recent arteriogram and with fasting serum cholesterol between 220 and 300 mg/dL were enrolled in a randomized, double-blind, placebo-controlled trial. All patients received intensive dietary counseling. Lovastatin or placebo was begun at 20 mg/d and was titrated to 40 and 80 mg during the first 16 weeks to attain a fasting low-density lipoprotein (LDL) cholesterol ≤130 mg/dL. The mean lovastatin dose was 36 mg/d. Coronary arteriography was repeated after 2 years. In 299 patients (90%), 3858 coronary segments containing 2309 stenoses were measured blindly on pairs of films with an automated computerized quantitative system. Total and LDL cholesterol decreased by 21±11% and 29±11%, respectively, in the lovastatin-treated group but changed by <2% in placebo patients. The primary end point, coronary change score, defined as the per-patient mean of the minimum lumen diameter changes (follow-up minus baseline angiogram) for all lesions measured, excluding those <25% on both films, worsened by 0.09±0.16 mm in the placebo group and by 0.05±0.13 mm in the lovastatin group (P= .01). Progression (a worsening in minimum diameter of one or more stenoses by.0.4 mm) with no regression at other sites occurred in 48 of 146 lovastatin and 76 of 153 placebo patients (33% versus 50%,P= .003). New coronary lesions developed in 23 lovastatin and 49 placebo patients (P= .001). The beneficial effect of treatment was most pronounced in the more numerous, milder lesions and in patients whose baseline total or LDL cholesterol levels were above the group median.ConclusionsLovastatin slows the progression of coronary atherosclerosis and inhibits the development of new coronary lesions.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundWe prospectively studied iron intake in relation to the incidence of coronary disease in a 4-year follow-up of 44 933 men (with no previous history of cardiovascular disease) aged 40 to 75 years in 1986 who completed a food frequency questionnaire at baseline.Methods and ResultsWe documented 844 incident cases of coronary disease (249 nonfatal myocardial infarctions, 137 coronary disease fatalities, and 458 bypass operations or angioplasties). After adjustment for established risk factors, there was no significant association between total iron intake and risk of coronary heart disease. Men in the highest quintile of total iron intake (median, 37 mg/d) had a relative risk (RR) of fatal coronary disease or nonfatal myocardial infarction of 0.73 (95% confidence intervals [CI], 0.51, 1.06) compared with men in the lowest quintile of intake (median, 11 mg/d). Dietary intake of heme iron – mainly from red meat – also not significantly associated with risk of coronary heart disease. However, incidence of fatal coronary disease or nonfatal myocardial infarction was higher among men in the top quintile of heme iron intake compared with men in the lowest quintile (RR, 1.42; 95% CI, 1.02, 1.98). This association remained after adjustment for dietary cholesterol and fats. Heme iron but not total iron intake was positively correlated with serum ferritin among 123 members of the cohort who participated in a validation study.ConclusionsThese results do not support the hypothesis that dietary iron in general increases coronary risk in men; they are consistent, however, with an increased risk of myocardial infarction among men with higher intake of heme iron, which is itself positively associated with iron stores.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundRecent clinical trials have shown that modification of plasma lipoprotein concentrations can favorably alter progression of coronary atherosclerosis, but no data exist on the effects of a comprehensive program of risk reduction involving both changes in lifestyle and medications. This study tested the hypothesis that intensive multiple risk factor reduction over 4 years would significantly reduce the rate of progression of atherosclerosis in the coronary arteries of men and women compared with subjects randomly assigned to the usual care of their physician.Methods and ResultsThree hundred men (n=259) and women (n=41) (mean age, 56±7.4 years) with angiographically defined coronary atherosclerosis were randomly assigned to usual care (n=155) or multifactor risk reduction (n=145). Patients assigned to risk reduction were provided individualized programs involving a low-fat and -cholesterol diet, exercise, weight loss, smoking cessation, and medications to favorably alter lipoprotein profiles. Computer-assisted quantitative coronary arteriography was performed at baseline and after 4 years. The main angiographic outcome was the rate of change in the minimal diameter of diseased segments. All subjects underwent medical and risk factor evaluations at baseline and yearly for 4 years, and reasons for all hospitalizations and deaths were documented. Of the 300 subjects randomized, 274 (91.3%) completed a follow-up arteriogram, and 246 (82%) had comparative measurements of segments with visible disease at baseline and follow-up. Intensive risk reduction resulted in highly significant improvements in various risk factors, including low-density lipoprotein cholesterol and apolipoprotein B (both, 22%), high-density lipoprotein cholesterol (+12%), plasma triglycerides (−20%), body weight (−4%), exercise capacity (+20%), and intake of dietary fat (−24%) and cholesterol (−40%) compared with relatively small changes in the usual-care group. No change was observed in lipoprotein(a) in either group. The risk-reduction group showed a rate of narrowing of diseased coronary artery segments that was 47% less than that for subjects in the usual-care group (change in minimal diameter, −0.024±0.066 mm/y versus −0.045±0.073 mm/y;P< .02, two-tailed). Three deaths occurred in each group. There were 25 hospitalizations in the risk-reduction group initiated by clinical cardiac events compared with 44 in the usual-care group (rate ratio, 0.61;P= .05; 95% confidence interval, 0.4 to 0.9).ConclusionsIntensive multifactor risk reduction conducted over 4 years favorably altered the rate of luminal narrowing in coronary arteries of men and women with coronary artery disease and decreased hospitalizations for clinical cardiac events.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

BackgroundWe investigated whether the greater increased risk of ischemic heart disease mortality associated with diabetes among women compared with men could be explained by their more pronounced lipoprotein abnormalities.Methods and ResultsSeventy-six men and 45 women with diabetes and 327 men and 496 women without diabetes were followed for an average of 16 years in a population-based study. Cox proportional hazards models were used to determine the relative hazard of ischemic heart disease mortality for changes in lipoprotein subfractions after adjustment for age, hypertension, obesity, smoking, exercise, alcohol consumption, and estrogen use (among women). The relative hazard of ischemic heart disease mortality among diabetic women was 1.76 (P= .10) for a 10-mg/dL decrement in highdensity lipoprotein cholesterol (HDL-C) and 3.13 (P= .01) for a 1-U increment in log, very-low-density lipoprotein cholesterol (VLDL-C). The risk of ischemic heart disease mortality among diabetic women relative to nondiabetic women for an HDL-C level of 50 mg/dL and a loge VLDL-C of 3 (about 20 mg/dL) were 4.1 and 3.4, respectively (P< .05). These lipoprotein changes were not associated with ischemic heart disease mortality among men or among nondiabetic women.ConclusionsExcess ischemic heart disease mortality among diabetic women is partially explained by deleterious levels of HDL-C and VLDL-C. HDL-C levels of ≤50 mg/dL and VLDL-C levels of ≥20 mg/dL appear to predict ischemic heart disease mortality among these women and may help identify women who would benefit most from intervention.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID