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Biomedical subjects

Frederick A Spencer

Publications and source records attributed to Frederick A Spencer.

At least 19 recordsLinked to original sources
PubMed2005

Trends in mortality attributed to heart failure in Worcester, Massachusetts, 1992 to 2001.

Sparse data are available, particularly from the more generalizable perspective of a population-based investigation, that describe recent trends in community death rates due to heart failure (HF). The objectives of this study were to describe a decade-long trend (1992 to 2001) in mortality attributed to HF among residents of the metropolitan area of Worcester, Massachusetts. A secondary study goal was to describe changes in death rates due to HF in men and in women, in subjects of different ages, and according to location of death. Death data tapes were obtained from the Massachusetts Department of Public Health for greater Worcester residents who died between 1992 and 2001. A total of 2,677 deaths from HF occurred in metropolitan Worcester residents between 1992 and 2001. Increases in crude death rates (per 100,000 population) attributed to HF were observed from 1992 (death rate 82) to 2001 (death rate 102). Adjustment for age attenuated the increase in community death rates due to HF. Slight increases in age-adjusted death rates from HF were noted in men, whereas age-adjusted mortality from HF in women decreased by 22% between our initial study year and the most recent study year. The elderly were at greatest risk for dying of HF and increases in HF death rates were observed in the oldest subjects (>/=85 years of age) over time. There was an increasing proportion of all deaths due to HF that occurred in the out-of-hospital setting in 2001 (61%) compared with 1992 (52%). The results of this study suggest changing patterns in death rates due to HF in a large northeastern community.

Aged↗
PubMed2005

Impact of combined pharmacologic treatment with clopidogrel and a statin on outcomes of patients with non-ST-segment elevation acute coronary syndromes: perspectives from a large multinational registry.

AIMS: To evaluate clinical outcomes associated with the combined use of clopidogrel and statins vs. clopidogrel alone on a background of aspirin therapy in patients with the spectrum of acute coronary syndromes (ACS). METHODS AND RESULTS: Utilizing data from the Global Registry of Acute Coronary Events, we studied 15 693 patients admitted with non-ST-segment elevation myocardial infarction (MI) or unstable angina, dividing them according to discharge medications: aspirin alone (group I); aspirin + clopidogrel (group II); aspirin + statin (group III); aspirin + clopidogrel + statin (group IV). Among the groups of patients in whom clopidogrel was used (groups II and IV), group II patients were older, more likely to have prior MI, but less likely to have a history of prior revascularization. In-hospital cardiac catheterization and revascularization rates were similar between groups II and IV. Importantly, Kaplan-Meier analysis showed that the 6 month mortality rate was lower in group IV (log-rank test 22.8, P<0.0001). The hazard ratio for the 6 month mortality rate was adjusted using the Cox proportional hazard model for confounding variables and for propensity score, and the 6 month mortality rate for patients in group IV remained lower compared with those in group II [0.59 (0.41-0.86), P<0.0001]. CONCLUSION: Our data suggest that the combination of clopidogrel with a statin has synergistic effects on the clinical outcomes of patients with non-ST-segment elevation ACS.

Adolescent↗
PubMed2004

A 25-year perspective into the changing landscape of patients hospitalized with acute myocardial infarction (the Worcester Heart Attack Study).

Over the past several decades, significant advances have been made in the primary and secondary prevention of coronary artery disease. However, effects of changing lifestyle and treatment practices on demographic and clinical profiles and on hospital outcomes of patients who present with acute myocardial infarction (AMI) have not been well characterized. We carried out a prospective population-based investigation of >25-year trends (1975 to 2001) in demographic and clinical characteristics, treatment practices, and hospital outcomes of patients who had been hospitalized with AMI. Residents of a metropolitan area (Worcester, Massachusetts) who had been hospitalized with validated AMI (n = 10,440) in all greater Worcester hospitals during thirteen 1-year periods between 1975 and 2001 comprised the sample of interest. Patients who had been hospitalized during the most recent study years were significantly older, were more likely to be women, and had a greater prevalence of co-morbidities. Hospitalized patients were increasingly more likely to receive effective cardiac medications and coronary interventions over the period under investigation. Multivariable-adjusted hospital survival rates improved considerably over time, whereas different trends were observed in the occurrence of several important clinical complications. The present results provide insights into the changing characteristics of patients who are hospitalized with AMI, treatment practices, and their short-term outcomes. Given the magnitude of AMI and evolving approaches to manage it, continued monitoring of these trends remains of considerable clinical and public health importance.

Adult↗
PubMed2004

Early withdrawal of statin therapy in patients with non-ST-segment elevation myocardial infarction: national registry of myocardial infarction.

BACKGROUND: There is increasing interest in the non-lipid-lowering effects of statins and their effect on outcomes in patients with acute coronary syndrome. It has been suggested that withdrawal of statin therapy during an acute coronary syndrome may attenuate any benefits of pretreatment, thereby providing indirect evidence of the importance of their non-lipid-lowering effects. METHODS: This observational study compared the demographic and clinical characteristics and hospital outcomes in patients with non-ST-segment elevation myocardial infarction enrolled in the National Registry of Myocardial Infarction 4. Comparison groups consisted of patients previously receiving statins who also received statins within 24 hours of hospital admission (n = 9,001), patients previously using statins in whom therapy was discontinued (n = 4,870), and patients who did not receive statins at any time before or during hospitalization (n = 54,635). RESULTS: Of 13,871 patients receiving statins before hospital admission, 35.1% had treatment withdrawn during the first 24 hours of hospitalization. These patients had increased hospital morbidity and mortality rates relative to patients in whom therapy was continued, with higher rates of heart failure, ventricular arrhythmias, shock, and death. In multivariate analyses, these patients were at statistically significant increased risk of hospital death compared with those continuing statin therapy and at similar risk compared with those not receiving statins before or during hospitalization. CONCLUSIONS: Withdrawal of statin therapy in the first 24 hours of hospitalization for non-ST-segment elevation myocardial infarction is associated with worse hospital outcomes. In the absence of data from randomized clinical trials, our findings suggest that statin therapy should be continued during hospitalization for myocardial infarction unless strongly contraindicated.

Aged↗
PubMed2004

Association of statin therapy with outcomes of acute coronary syndromes: the GRACE study.

BACKGROUND: Statins administered early in patients with acute coronary syndromes may lead to modest reductions in recurrent ischemic events. OBJECTIVE: To examine the association between previous and early in-hospital statin therapy and the presentation and outcomes of an acute coronary syndrome. DESIGN: Cohort study. SETTING: 94 hospitals in 14 countries participating in the Global Registry of Acute Coronary Events (GRACE). PATIENTS: 19,537 patients with an acute coronary syndrome who were enrolled from April 1999 to September 2002. MEASUREMENTS: Statin use before and after presentation with an acute coronary syndrome and associated rates of myocardial infarction, hospital complications, and hospital mortality. The composite end point included death, in-hospital myocardial infarction, and stroke. RESULTS: Patients who were already taking statins when they presented to the hospital were less likely to have ST-segment elevation (odds ratio [OR], 0.79 [95% CI, 0.71 to 0.88]) or myocardial infarction (OR, 0.78 [CI, 0.70 to 0.86]). Patients who continued to take statins in the hospital were less likely to experience complications or die than patients who never received statins (OR, 0.66 [CI, 0.56 to 0.77]). Patients not previously taking statins who began statin therapy in the hospital were less likely to die than patients who never received statin therapy (OR, 0.38 [CI, 0.30 to 0.48]). However, adjustment for the hospital of admission attenuated the association between initiation of statin therapy and the composite end point (OR, 0.84 [CI, 0.65 to 1.10]). LIMITATIONS: This observational study cannot exclude confounding by clinical and hospital factors. CONCLUSIONS: These data support the hypothesis that statin therapy can modulate early pathophysiologic processes in patients with acute coronary syndromes. A randomized trial of statin therapy in acute myocardial infarction is warranted.

Age Factors↗
PubMed2004

Declining length of hospital stay for acute myocardial infarction and postdischarge outcomes: a community-wide perspective.

BACKGROUND: The objectives of this population-based study were to describe trends of more than a decade (1986-1999) in duration of hospitalization after acute myocardial infarction (AMI), patient characteristics associated with varying lengths of stay, and the impact of declining length of stay on postdischarge mortality. METHODS: The study sample consisted of 4551 patients discharged after AMI from all greater Worcester, Mass, hospitals in 8 annual periods during the study period. Regression models were used to examine the influence of demographic, clinical, and treatment variables on length of stay and the association between declining length of hospital stay and postdischarge mortality. RESULTS: Marked declines were observed in the average length of stay between the 1986-1988 (11.7 days) and 1997-1999 (5.9 days) periods. Factors associated with a longer hospital stay included advanced age, female sex, anterior and Q-wave MI, and occurrence of clinically important cardiac complications. Patients with health maintenance organization, Medicare, Medicaid, or no insurance coverage were less likely to have an increased length of stay. Increased 30- and 90-day mortality was associated with a length of stay of greater than 14 days (odds ratio, 2.08; 95% confidence interval, 1.18-3.66) relative to those with a length of stay of 6 to 8 days (odds ratio, 2.01; 95% confidence interval, 1.34-3.01). Patients with a length of stay of less than 6 days exhibited no significant increases in postdischarge mortality. Similar trends were observed in patients with a complicated AMI. CONCLUSIONS: We found marked decreases in length of stay for patients hospitalized with AMI during the past decade. However, we found no negative association between declining length of stay and short-term mortality after hospital discharge for AMI.

Aged↗
PubMed2004

Vascular endothelial tissue factor pathway inhibitor kinetics in culture following exposure to DX-9065a--a selective and direct factor Xa inhibitor.

BACKGROUND: Tissue factor (TF), a membrane-bound glycoprotein that initiates blood coagulation by allosteric activation of factor (f) VII, is regulated predominantly by tissue factor pathway inhibitor (TFPI). Because vascular endothelial cells synthesize and constitutively secrete TFPI and fXa may directly influence its cellular clearance, we sought to determine the effects of DX-9065a, a direct and selective fXa inhibitor, on TFPI kinetics in culture. METHODS/RESULTS: Human umbilical vein endothelial cells were grown to confluence and incubated with unfractionated heparin (1.0 U/mL), enoxaparin (1.5 U/mL), or DX-9065a at low (10 ng/ml), moderate (30 ng/ml), or high (90 ng/ml) concentrations. Compared to control, increases in TFPI were seen with both unfractionated heparin (182% higher, p < 0.001) and enoxaparin (194% higher, p < 0.001). Low concentration DX-9065a did not increase TFPI levels above control (0.8% higher, p = 0.91). In contrast, moderate and high concentrations produced 124% higher (p < 0.001) and 198% higher (p < 0.001) TFPI concentrations than control, respectively. CONCLUSIONS: DX-9065a increases vascular endothelial cell TFPI concentrations in human tissue culture. Although the mechanism has yet to be established, decreased fXa availability may limit fXa-TFPI complex formation and its subsequent cellular uptake. Whether increased surface TFPI contributes to the overall anticoagulant profile of DX-9065a will require further investigation.

Antithrombin III↗
PubMed2003

Trends (1986 to 1999) in the incidence and outcomes of in-hospital stroke complicating acute myocardial infarction (The Worcester Heart Attack Study).

Although stroke is an infrequent hospital complication of acute myocardial infarction (AMI), limited contemporary data are available about the incidence and death rates associated with this serious complication. The objective of this population-based study was to examine temporal trends (1986 to 1999) in the risk of stroke and associated hospital outcomes in patients hospitalized with AMI. This was an observational study of 6,325 metropolitan Worcester, Massachusetts, residents hospitalized with validated AMI and without prior stroke at all greater Worcester hospitals during 8 one-year periods between 1986 and 1999. Overall, 1.5% of patients (n = 92) with confirmed AMI developed an acute stroke during their index hospitalization. Decreases, followed by increases, in the risk of acute stroke were observed between 1986 and 1999. The highest risk for stroke was observed in the most recent study year of 1999 (3.0%). Several demographic, medical history, and clinical characteristics were associated with an increased risk of stroke overall and separately in younger and older patients hospitalized with AMI. Patients developing an acute stroke had a significantly increased risk of dying during hospitalization even after controlling for other factors of prognostic importance (adjusted odds ratio 4.26, 95% confidence interval 2.49 to 7.31). The results of this community-wide study provide insights into recent trends in the development of acute stroke after AMI and into the profile of high-risk patients.

Aged↗
PubMed2003

Risk factors for venous thromboembolism.

Until the 1990s, venous thromboembolism (VTE) was viewed primarily as a complication of hospitalization for major surgery (or associated with the late stage of terminal illness). However, recent trials in patients hospitalized with a wide variety of acute medical illnesses have demonstrated a risk of VTE in medical patients comparable with that seen after major general surgery. In addition, epidemiologic studies have shown that between one quarter and one half of all clinically recognized symptomatic VTEs occur in individuals who are neither hospitalized nor recovering from a major illness. This expanding understanding of the population at risk challenges physicians to carefully examine risk factors for VTE to identify high-risk patients who could benefit from prophylaxis. Factors sufficient by themselves to prompt physicians to consider VTE prophylaxis include major surgery, multiple trauma, hip fracture, or lower extremity paralysis because of spinal cord injury. Additional risk factors, such as previous VTE, increasing age, cardiac or respiratory failure, prolonged immobility, presence of central venous lines, estrogens, and a wide variety of inherited and acquired hematological conditions contribute to an increased risk for VTE. These predisposing factors are seldom sufficient by themselves to justify the use of prophylaxis. Nevertheless, individual risk factors, or combinations thereof, can have important implications for the type and duration of appropriate prophylaxis and should be carefully reviewed to assess the overall risk of VTE in each patient.

Humans↗
PubMed2003

Plasmin-mediated proteolysis of vascular endothelial cell heparin releasable tissue factor pathway inhibitor.

BACKGROUND: Fibrinolytic therapy represents a widely available and effective treatment modality for ST segment elevation myocardial infarction (MI). Its overall benefit is attenuated by a high incidence of coronary arterial reocclusion. METHODS/RESULTS: Human umbilical vein endothelial cells (HUVEC) were incubated with unfractionated heparin (1.5 U/ml) (to provoke tissue factor pathway inhibitor [TFPI] release) followed by the addition of varying concentrations of alteplase (recombinant tissue plasminogen activator), plasminogen, their combination or plasmin alone. In the presence of 20% TFPI-depleted human plasma, there was a concentration-dependent decrease in TFPI levels following incubation with alteplase (28% reduction at 200 ng/ml; P < 0.01); 37% reduction at 1000 ng/ml (P < 0.001). Similar effects were observed for alteplase combined with plasminogen (P < 0.001), plasmin alone (P < 0.001) and with HUVEC incubated with low concentrations of plasmin (10 ng/ml) prior to heparin exposure. CONCLUSIONS: Plasmin, a non-specific protease, degrades vascular endothelial cell (constitutive) TFPI and heparin-releasable TFPI, attenuating an important pathway of vascular surface thromboresistance and potentially contributing to coronary arterial reocclusion after fibrinolytic therapy.

Coronary Artery Disease↗
PubMed2003

Two-decade-long trends (1975-1997) in the incidence, hospitalization, and long-term death rates associated with complete heart block complicating acute myocardial infarction: a community-wide perspective.

BACKGROUND: The purpose of this community-wide study was to describe a >2-decade-long experience (1975-97) in the incidence and death rates associated with complete heart block (CHB) in patients with acute myocardial infarction (AMI). Limited population-based data exist describing recent, and changes with time therein, incidence and case-fatality rates associated with CHB complicating AMI. METHODS: We conducted an observational study of 9082 metropolitan Worcester, Mass, residents (1990 census = 437,000) hospitalized with validated AMI in all greater Worcester hospitals during 11 1-year periods between 1975 and 1997. RESULTS: Overall, CHB developed in 5.0% of patients with AMI. The incidence rates of CHB declined in the periods studied (6.0% in 1975/78 vs 3.1% in 1997). Declines in the occurrence of CHB were noted in patients with anterior or inferior/posterior MI. These trends remained after adjustment for other factors that might affect the risk of CHB. Patients in whom CHB developed experienced significantly higher hospital death rates than patients in whom CHB did not develop (46.8% vs 14.6%). However, improving trends in the hospital survival rate of patients with CHB were observed between 1975/78 (47.4% surviving) and 1997 (61.3% surviving). Patients in whom CHB developed during hospitalization were not at increased risk for dying after hospital discharge. CONCLUSIONS: Our findings indicate that the incidence of CHB complicating AMI has declined with time. The hospital prognosis of patients in whom CHB developed has improved, but these patients remain at an increased risk of hospital mortality. The long-term prognosis of patients with inferior MI and CHB is similar to that of patients in whom CHB did not develop. Patients with anterior MI and CHB may be at an increased risk of long-term mortality.

Acute Disease↗
PubMed2002

Impact of aspirin on presentation and hospital outcomes in patients with acute coronary syndromes (The Global Registry of Acute Coronary Events [GRACE]).

The long-term use of aspirin (ASA) reduces the risk of subsequent acute coronary syndromes in patients with coronary artery disease (CAD). It is less clear whether ASA therapy benefits patients who develop an acute coronary syndrome despite its use. Baseline characteristics, type of acute coronary syndrome, and in-hospital events were compared on the basis of previous use of ASA in 11,388 patients with and without a history of CAD presenting to 94 multinational hospitals. A total of 73.0% of patients with a history of CAD (n = 4,974) were previously on long-term ASA therapy compared with 19.4% of patients without a history of CAD (n = 6,414). After multivariate regression analysis controlling for various potentially confounding factors, patients with a history of CAD who were previously taking ASA were significantly less likely to present with ST-segment elevation myocardial infarction (MI) (adjusted odds ratio [OR] 0.52, 95% confidence intervals [CI] 0.44 to 0.61) or die during hospitalization (OR 0.69, 95% CI 0.50 to 0.95) in comparison to patients who were not taking ASA. Patients without a history of CAD and who were previously taking ASA also had a lower risk of developing ST-segment elevation MI (OR 0.35, 95% CI 0.30 to 0.40) and a trend toward a decreased hospital death rate (OR 0.77, 95% CI 0.55 to 1.07). These results demonstrate that patients with a history of CAD who present with an acute coronary syndrome despite prior ASA use have less severe clinical presentation, fewer hospital complications, and lower in-hospital death rates than patients not previously taking ASA.

Aged↗
PubMed2002

Heterogeneity in the management and outcomes of patients with acute myocardial infarction complicated by heart failure: the National Registry of Myocardial Infarction.

BACKGROUND: Heart failure (HF) is an important predictor of poor outcome after acute myocardial infarction (AMI). However, limited data exist about the clinical significance of HF in the coronary reperfusion era and the impact of its timing on hospital outcomes. The objective of this study was to determine the clinical impact of HF complicating AMI in the National Registry of Myocardial Infarction (NRMI). A secondary objective was to determine differences in demographic and clinical characteristics, treatment, and hospital death rates in patients presenting with HF compared with those developing HF after presentation. METHODS AND RESULTS: The study sample consisted of patients with AMI and without a history of HF included in the NRMI. Of 606 500 cases included from July 1, 1994 to June 30, 2000, 123 938 (20.4%) patients had HF at the time of hospital presentation and 52 220 (8.6%) developed HF thereafter. Patients with HF were older, more likely female, had more comorbidities, and were less likely to receive effective cardiac medications compared with patients without HF. The multivariable adjusted odds for in-hospital death were higher for patients with HF at presentation and thereafter (3.1 and 5.5, respectively) than those without HF. CONCLUSIONS: Results from this nationwide registry suggest that the incidence and hospital death rates associated with HF complicating AMI remain high. Patients developing HF after hospital admission are at even greater risk than those presenting with HF. Effective cardiac therapies remain underutilized in these patients, and the reasons for this underutilization need to be explored.

Aged↗
PubMed2002

Comparative effects of unfractionated heparin and low molecular weight heparin on vascular endothelial cell tissue factor pathway inhibitor release: a model for assessing intrinsic thromboresistance.

OBJECTIVES: The purpose of our study was to characterize tissue factor pathway inhibitor (TFPI) release from human vascular endothelial cells following daily exposure to varying concentrations of unfractionated heparin (UFH) and low molecular weight heparin (LMWH). BACKGROUND: A "rebound" increase in ischemic/thrombotic events, including myocardial infarction and cardiovascular death, has been observed after the abrupt cessation of UFH. In a single center pilot study of patients with acute coronary syndromes (ACS) we reported that thrombin generation was evident within one (1) hour of UFH cessation, increased progressively over the subsequent 24 hours, correlated directly with factor VII activity and inversely with TFPI (concentration and activity). METHODS: Human umbilical vein endothelial cells were grown to confluence and incubated with varying concentrations of UFH or dalteparin, a low molecular weight haparin, for up to 144 hours. Daily samples of the cells supernatant were obtained and assayed for TFPI. Cellular reserve and responsiveness to recombinant endothelial cell growth factor (rEGF) stimulation were determined at 168 hours. RESULTS: In low concentrations (0.5 U/mL) UFH caused a progressive rise in TFPI concentration with a peak level of 6.36 +/- 0.5 ng/10(5) cells at 24 hours. By 72 hours of daily exposure, the levels declined to below control values and TFPI release following rEGF stimulation was reduced by approximately 60% compared to control (1.93 +/- 0.42 vs 4.3 +/- 0.78 ng/10(5) cells; p = 0.001). Initial endothelial cell release and rate of decline were more robust with high concentrations of UFH (5.0 U/ml). TFPI levels were above control values at each sampling time point up to 120 hours and cellular responsiveness to stimulation was preserved with dalteparin (compared to UFH) (p < 0.001). CONCLUSIONS: Thrombin generation and clinical events that occur during treatment with UFH and following its abrupt cessation may represent an acquired state of transiently impaired thromboresistance to the tissue factor-VIIa complex. The differing effects of UFH and LMWH on vascular endothelial cell TFPI synthesis, release and reserve with prolonged administration require further investigation.

Cells, Cultured↗