摘要:

BackgroundMuscle sympathetic nerve activity (MSNA) is increased in patients with obstructive sleep apnea (OSA). We tested the hypothesis that tonic activation of excitatory chemoreceptor afferents contributes to the elevated sympathetic activity in OSA.Methods and Results-Using a double-blind, randomized, vehicle-controlled design, we examined the effects of chemoreflex deactivation (by comparing effects of breathing 100% oxygen for 15 minutes with effects of breathing room air for 15 minutes) on MSNA, heart rate, blood pressure, and minute ventilation in 14 untreated patients with OSA and in 12 normal subjects matched for age and body mass index. All control subjects underwent overnight polysomnography to exclude the existence of occult OSA. Baseline MSNA was markedly elevated in the patients with OSA compared with the control subjects (44 +/- 4 versus 30 +/- 3 bursts per minute; P = .01). In both control subjects and patients with OSA, heart rate decreased during administration of 100% oxygen but did not change during administration of room air. By contrast, both MSNA (P = .008) and mean arterial pressure (P = .02) were significantly reduced during chemoreflex deactivation by 100% oxygen only in patients with OSA but not in control subjects.ConclusionsTonic activation of excitatory chemoreflex afferents may contribute to increased efferent sympathetic activity to muscle circulation in patients with OSA. (Circulation. 1998;97:943-945.)

ISSN:0009-7322    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

BackgroundWe determined the effect of incorporating the results of eight recently published trials of Hmg CoA reductase inhibitors ("statins") on the conclusions from our previously published meta-analysis regarding the clinical benefit of cholesterol lowering.Methods and Results-We used the same analytic approach as in our previous investigation, separating the specific effects of cholesterol lowering from the effects attributable to the different types of intervention studied. The reductions in coronary heart disease (CHD) and total mortality risk observed for the statins fell near the predictions from our earlier meta-analysis. Including the statin trial findings into the calculations led to a prediction that for every 10 percentage points of cholesterol lowering, CHD mortality risk would be reduced by 15% (P <.001), and total mortality risk would be reduced by 11% (P < .001), as opposed to the values of 13% and 10%, respectively, reported previously. Cholesterol lowering in general and by the statins in particular does not increase non-CHD mortality risk.ConclusionsAdding the results from the statin trials confirmed our original conclusion that lowering cholesterol is clinically beneficial. The relationships (slope) between cholesterol lowering and reduction in CHD and total mortality risk became stronger, and the standard error of the estimated slopes decreased by about half. Use of statins does not increase non-CHD mortality risk. The effect of the statins on CHD and total mortality risk can be explained by their lipid-lowering ability and appears to be directly proportional to the degree to which they lower lipids. (Circulation. 1998;97:946-952.)

ISSN:0009-7322    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

BackgroundHypercholesterolemia is considered a major risk factor for the development of atherosclerosis. Enhanced lipid peroxidation and persistent platelet activation can be observed in vivo in hypercholesterolemic patients and may have pathophysiological implications in the occurrence of cardiovascular events. P-selectin may play an important role in the pathogenesis of multicellular events, including atherosclerosis. We studied the impact of hypercholesterolemia and oxidative stress on plasma levels of P-selectin.Methods and Results-Plasma levels of P-selectin were measured by means of an enzyme immunoassay in 20 hypercholesterolemic patients with no clinical evidence of cardiovascular disease and in 20 sex- and age-matched normocholesterolemic subjects. Hypercholesterolemic patients had higher levels of P-selectin compared with that of control subjects (98 +/- 61 versus 56 +/- 14 ng/mL; P = .001). They also displayed increased von Willebrand Factor (vWF) levels (176 +/- 22 versus 119 +/- 12%; P = .0001). A direct correlation was observed between P-selectin and LDL cholesterol levels (p = .453). Administration of vitamin E (600 mg/d for 2 weeks) to hypercholesterolemic patients significantly reduced plasma P-selectin (40%), and an inverse correlation was observed between vitamin E and P-selectin plasma levels (p = -.446).ConclusionsHypercholesterolemia is associated with elevated plasmatic P-selectin. Altered oxidative processes leading to endothelial dysfunction and persistent platelet activation may contribute to increased soluble P-selectin levels. P-selectin may be proposed as a marker of endothelial dysfunction in hypercholesterolemic patients. (Circulation. 1998;97:953-957.)

ISSN:0009-7322    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

BackgroundSeveral studies have indicated that a variety of social relationships are important predictors of morbidity and mortality in patients with coronary artery disease, but little attention has been focused on the prognostic importance of these factors in the growing population of elderly patients with heart failure. To address this issue, we sought to determine whether emotional support is associated with fatal and nonfatal cardiovascular events in elderly patients hospitalized with heart failure.or= to 65 years who were hospitalized with clinical heart failure and were part of the New Haven, Conn, cohort of the Established Population for the Epidemiologic Study of the Elderly, a longitudinal, community-based study of aging that included a comprehensive assessment of psychosocial support. In the unadjusted analysis, lack of emotional support was significantly associated with the 1-year risk of fatal and nonfatal cardiovascular outcomes [odds ratio, 2.4; 95% confidence interval, 1.1 to 4.9]. After adjustment for demographic factors, clinical severity, comorbidity and functional status, social ties, and instrumental support, the absence of emotional support remained associated with a significantly higher risk (odds ratio, 3.2; 95% confidence interval, 1.4 to 7.8). The test for interaction between emotional support and sex was significant (P = .01). In the fully adjusted model, the odds ratio for women was 8.2 (95% confidence interval, 2.5 to 27.2) compared with 1.0 (95% confidence interval, 0.3 to 3.3) for men.ConclusionsAmong elderly patients hospitalized with clinical heart failure, the absence of emotional support, measured before admission, is a strong, independent predictor of the occurrence of fatal and nonfatal cardiovascular events in the year after admission. In this cohort, the association is restricted to women. (Circulation. 1998;97:958-964.)

ISSN:0009-7322    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

BackgroundParoxysmal atrial fibrillation (PAF) is considered a frequent complication of acute myocardial infarction (AMI), associated with increased in-hospital and long-term mortality rates. This notion is based on data collected before thrombolysis and additional modern methods of treatment became widely available, and no information is available on the significance of PAF in the general population with AMI in the thrombolytic era. The aim of the present study was to define the incidence, associated clinical parameters, and short- and long-term prognostic significance of PAF in patients with AMI in the thrombolytic era.Methods and Results-A prospective, nationwide survey was conducted of 2866 consecutive patients admitted with AMI in all 25 coronary care units in Israel during January/February 1992, 1994, and 1996 (thrombolytic era [TE]). The data were compared with a previous Israeli study of 5803 patients with AMI hospitalized in 1981 through 1983 (prethrombolytic era [PTE]). Patients in the TE with PAF were older and had a worse risk profile than those without PAF. PAF in the TE was independently associated with increased 30-day (odds ratio, 1.32; 95% confidence interval, 0.92 to 1.87) and 1-year (relative risk, 1.33; 95% confidence interval, 1.05 to 1.68) mortality rates. The incidence of PAF (8.9% and 9.9%) and the 30-day (25.1% and 27.6%) and 1-year (38.4% and 42.5%) mortality rates of patients with PAF were similar in the TE and PTE, although PAF in the TE occurred in older and sicker patients than those in the PTE. After adjustment for conventional risk factors, PAF was associated with significantly lower 30-day (odds ratio, 0.64; 95% confidence interval, 0.44 to 0.94) and 1-year (relative risk, 0.69; 95% confidence interval, 0.54 to 0.88) mortality rates compared with the PTE.ConclusionsPatients with AMI who develop PAF in the TE have significantly worse short- and long-term prognoses than patients without PAF, mostly due to their worse risk profile. After adjustment for confounding factors, patients with PAF in the TE have a better overall outcome than counterparts in the PTE, probably reflecting the better management of patients with AMI in the TE. (Circulation. 1998;97:965-970.)

ISSN:0009-7322    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

BackgroundWe compared cardiac mast cell (HHMC) density and the immunological and nonimmunological release of mediators from mast cells isolated from heart tissue of patients with idiopathic dilated (DCM) (n = 24) and ischemic cardiomyopathy (ICM) (n = 10) undergoing heart transplantation and from control subjects (n = 10) without cardiovascular disease.Methods and Results-HHMC density in DCM (18.4 +/- 1.6 cells/mm2) and ICM (18.4 +/- 1.5 cells/mm2) was higher than that in control hearts (5.3 +/- 0.7 cells/mm2; P < .01). The histamine and tryptase contents of DCM and ICM hearts were higher than those of control hearts. The histamine content of the hearts was correlated with mast cell density (rs= .91; P < .001). Protein A/gold staining of heart tissue revealed stem cell factor (SCF), the principal growth, differentiating, and activating factor of human mast cells, in HHMC secretory granules. Histamine release from cardiac mast cells caused by immunological (anti-IgE and rhSCF) and nonimmunological stimuli (Ca2+ionophore A23187) was higher in patients with DCM and ICM compared with control subjects. Immunological activation of HHMC induced a significantly greater release of tryptase and LTC4in patients with DCM and ICM compared with control subjects.ConclusionsHistamine and tryptase content and mast cell density are higher in failing hearts than in control hearts. SCF, present in secretory granules of HHMC, might represent an autocrine factor sustaining mast cell hyperplasia in heart tissue in these patients. The increased local release of fibrogenic factors (eg, histamine, tryptase, and leukotriene C4) might contribute to collagen accumulation in the hearts of patients with cardiomyopathy. (Circulation. 1998;97:971-978.)

ISSN:0009-7322    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

BackgroundPostmenopausal hormone therapy has been reported to decrease levels of lipoprotein (Lp)(a) in cross-sectional studies and small or short-term longitudinal studies. We report findings from a large, prospective, placebo-controlled clinical trial that allows a broad characterization of these effects for four regimens of hormone therapy.Methods and Results-The Postmenopausal Estrogen/Progestin Interventions study was a 3-year, placebo-controlled, randomized clinical trial to assess the effect of hormone regimens on cardiovascular disease risk factors in postmenopausal women 45 to 65 years of age. The active regimens were conjugated equine estrogens therapy at 0.625 mg daily, alone or in combination with each of three regimens of progestational agents: medroxyprogesterone acetate (MPA) at 2.5 mg daily (ie, continuous MPA), MPA at 10 mg days 1 to 12 (ie, cyclical MPA), and micronized progesterone at 200 mg days 1 to 12. Plasma levels of Lp(a) were measured at baseline (n = 366), 12 months (n = 354), and 36 months (n = 342). Assignment to hormone therapy resulted in a 17% to 23% average drop in Lp (a) concentrations relative to placebo (P < .0001), which was maintained across 3 years of follow-up. No significant differences were observed among the four active arms. Changes in Lp(a) associated with hormone therapy were positively correlated with changes in LDL cholesterol, total cholesterol, apolipoprotein B, and fibrinogen levels and were similar across subgroups defined by age, weight, ethnicity, and prior hormone use.ConclusionsPostmenopausal estrogen therapy, with or without concomitant progestin regimens, produces consistent and sustained reductions in plasma Lp (a) concentrations. (Circulation. 1998;97:979-986.)

ISSN:0009-7322    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

BackgroundIn patients with sick sinus syndrome, choice of pacing mode has been implicated in the development of congestive heart failure.Methods and Results-A total of 225 consecutive patients with sick sinus syndrome and intact atrioventricular conduction were randomized to either single-chamber atrial pacing (n = 110) or single-chamber ventricular pacing (n = 115). Clinical assessment included New York Heart Association classification, medication, and M-mode echocardiography before pacemaker implantation, after 3 months, and subsequently once every year. At long-term follow-up (mean, 5.5 +/- 2.4 years), NYHA class was higher in the ventricular group than in the atrial group (NYHA class I/II/III/IV: 65/44/4/0 versus 84/22/2/1 patients, P = .010). Increase in NYHA class during follow-up was observed in 35 of 113 patients in the ventricular group versus 10 of 109 in the atrial group (P < .0005). Increase in dose of diuretics from randomization to last follow-up was significantly higher in the ventricular group than in the atrial group (21 +/- 49 versus 8 +/- 42 mg furosemide/d, P = .033). The left ventricular fractional shortening decreased significantly in the ventricular group (from 0.36 +/- 0.12 to 0.31 +/- 0.08, P < .0005) but not in the atrial group (from 0.35 +/- 0.13 to 0.33 +/- 0.09, P = .087). The left atrial diameter increased significantly in both treatment groups (ventricular group: from 34 +/- 7 to 41 +/- 7 mm, P < .0005; atrial group: from 34 +/- 6 to 37 +/- 7 mm, P = .002), but the increase was significantly higher in the ventricular group than in the atrial group (P < 0005).ConclusionsDuring long-term follow-up, ventricular pacing is associated with a higher incidence of congestive heart failure and consumption of diuretics than atrial pacing. This is accompanied by a decrease in left ventricular fractional shortening and an increased dilatation of the left atrium in the ventricular paced patients. (Circulation. 1998;97:987-995.)

ISSN:0009-7322    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

BackgroundOur purposes were to estimate the strength of the longitudinal relationship between hyperinsulinemia and cardiovascular diseases (CVD) from the available literature and to identify study characteristics that modify this relationship.Methods and Results-Articles were identified by means of a MEDLINE and Embase search and citation tracking. Eligible studies were prospective population-based cohort studies and nested case-control studies on the relationship between, on the one hand, fasting or nonfasting insulin levels and, on the other hand, myocardial infarction, death from coronary heart disease, and/or ECG abnormalities. Data were extracted pertaining to insulin measurements, type of outcome studied, adjustment for confounding, sex, mean age of the study population, follow-up period, insulin assay, and ethnic background (white or nonwhite). Associations of insulin and CVD were reexpressed in a uniform manner, an estimate of relative risk (RR) and 95% CI, to be used in meta-regression analyses. Twelve of 17 potentially eligible articles provided sufficient information. Overall, a weak positive association was found. The meta-analysis resulted in an estimated summary RR (95% CI) of 1.18 (1.08 to 1.29) for differences in insulin level, equivalent to the difference between the 75th and the 25th percentiles of the general population in the Netherlands. Ethnic background and type of insulin assay modified the relationship between insulin and CVD with borderline significance.ConclusionsHyperinsulinemia is a weak risk indicator for the occurrence of CVD. The relationship between hyperinsulinemia and CVD was modified by ethnic background and by the type of insulin assay involved. (Circulation. 1998;97:996-1001.)

ISSN:0009-7322    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

BackgroundPlatelet-rich arterial thrombi are resistant to lysis by plasminogen activators. However, the mechanisms underlying thrombolysis resistance are poorly defined. Plasminogen activator inhibitor-1 (PAI-1), which is present in plasma, platelets, and vascular endothelium, may be an important determinant of the resistance of arterial thrombi to lysis. However, in vitro studies examining the regulation of platelet-rich clot lysis by PAI-1 have yielded inconsistent results.Methods and Results-We developed a murine arterial injury model and applied it to wild-type (PAI-1 +/+) and PAI-1-deficient (PAI-1 -/-) animals. FeCl3was used to induce carotid artery thrombosis. Thrombi consisted predominantly of dense platelet aggregates, consistent with the histology of thrombi in large-animal arterial injury models and human acute coronary syndromes. To examine the role of PAI-1 in regulating endogenous clearance of platelet-rich arterial thrombi, thrombi were induced in 22 PAI-1 +/+ mice 14 PAI-1 -/- mice. Twenty-four hours later, the amount of residual thrombus was determined by histological analysis of multiple transverse sections of each artery. Residual thrombus was detected in 55 of 85 sections (64.7%) obtained from PAI-1 +/+ mice compared with 19 of 56 sections (33.9%) from PAI-1 -/- mice (P = .009). Computer-assisted planimetry analysis revealed that mean thrombus cross-sectional area was 0.033 +/- 0.027 mm2in PAI-1 +/+ mice versus 0.016 +/- 0.015 mm2in PAI-1 -/- mice (P = .048).ConclusionsPAI-1 is an important determinant of thrombolysis at sites of arterial injury. Application of this model to other genetically altered mice should prove useful for studying the molecular determinants of arterial thrombosis and thrombolysis. (Circulation. 1998;97:1002-1008.)

ISSN:0009-7322    

出版商:OVID    

年代:1998

数据来源: OVID