Frederick A. Spencer

Seasonal Distribution of Acute Myocardial Infarction in the Second National Registry of Myocardial Infarction

OBJECTIVES This observational study sought to determine whether cases of acute myocardial infarction (AMI) reported to the second National Registry of Myocardial Infarction (NRMI-2) varied by season. BACKGROUND The existence of circadian variation in the onset of AMI is well established. Examination of this periodicity has led to new insights into pathophysiologic triggers of atherosclerotic plaque rupture. Although a seasonal pattern for mortality from AMI has been previously noted, it remains unclear whether the occurrence of AMI also displays a seasonal rhythmicity. Documentation of such a pattern may foster investigation of new pathophysiologic determinants of plaque rupture and intracoronary thrombosis. METHODS We analyzed the number of cases of AMI reported to NRMI-2 by season during the period July 1, 1994 to July 31, 1996. Data were normalized so that seasonal occurrence of AMI was reported according to a standard 90-day length. RESULTS A total of 259,891 cases of AMI were analyzed during the study period. Approximately 53% more cases were reported in winter than during the summer. The same seasonal pattern (decreasing occurrence of reported cases from winter to fall to spring to summer) was seen in men and women, in different age groups and in 9 of 10 geographic areas. In-hospital case fatality rates for AMI also followed a seasonal pattern, with a peak of 9% in winter. CONCLUSION The present results suggest that there is a seasonal pattern in the occurrence of AMIs reported to NRMI-2 that is characterized by a marked peak of cases in the winter months and a nadir in the summer months. This pattern was seen in all subgroups analyzed as well as in different geographic areas. These findings suggest that the chronobiology of seasonal variation in AMI may be affected by variables independent of climate.

Recent Trends in the Incidence, Treatment, and Outcomes of Patients with STEMI and NSTEMI

BACKGROUND despite the widespread use of electrocardiographic changes to characterize patients presenting with acute myocardial infarction, little is known about recent trends in the incidence rates, treatment, and outcomes of patients admitted for acute myocardial infarction further classified according to the presence of ST-segment elevation. The objectives of this population-based study were to examine recent trends in the incidence and death rates associated with the 2 major types of acute myocardial infarction in residents of a large central Massachusetts metropolitan area. METHODS We reviewed the medical records of 5383 residents of the Worcester (MA) metropolitan area hospitalized for either ST-segment elevation acute myocardial infarction (STEMI) or non-ST-segment acute myocardial infarction (NSTEMI) between 1997 and 2005 at 11 greater Worcester medical centers. RESULTS the incidence rates (per 100,000) of STEMI decreased appreciably (121 to 77), whereas the incidence rates of NSTEMI increased slightly (126 to 132) between 1997 and 2005. Although in-hospital and 30-day case-fatality rates remained stable in both groups, 1-year postdischarge death rates decreased between 1997 and 2005 for patients with STEMI and NSTEMI. CONCLUSIONS the results of this study demonstrate recent decreases in the magnitude of STEMI, slight increases in the incidence rates of NSTEMI, and decreases in long-term mortality in patients with STEMI and NSTEMI. Our findings suggest that acute myocardial infarction prevention and treatment efforts have resulted in favorable decreases in the frequency of STEMI and death rates from the major types of acute myocardial infarction.

30-Year Trends in Heart Failure in Patients Hospitalized With Acute Myocardial Infarction

Despite significant advances in its treatment, acute myocardial infarction (AMI) remains an important cause of heart failure (HF). Contemporary data remain lacking, however, describing long-term trends in incidence rates, demographic and clinical profiles, and outcomes of patients who develop HF as a complication of AMI. Our study sample consisted of 11,061 residents of the Worcester (Massachusetts) metropolitan area hospitalized with AMI at all greater Worcester hospitals in 15 annual study periods from 1975 to 2005. Overall, 32.4% of patients (n = 3,582) with AMI developed new-onset HF during their acute hospitalization. Patients who developed HF were generally older, more likely to have pre-existing cardiovascular disease, and were less likely to receive cardiac medications or undergo revascularization procedures during their hospitalization than patients who did not develop HF (p <0.001). Incidence rates of HF remained relatively stable from 1975 to 1991 at 26% but decreased thereafter. Decreases were also noted in hospital and 30-day death rates in patients with acute HF (p <0.001). However, patients who developed new-onset HF remained at significantly higher risk for dying during their hospitalization (21.6%) than patients who did not develop this complication (8.3%, p <0.001). Our large community-based study of patients hospitalized with AMI demonstrates that incidence rates of and mortality attributable to HF have decreased over the previous 3 decades. In conclusion, HF remains a common and frequently fatal complication of AMI to which increased surveillance and treatment efforts should be directed.

Thirty-Year (1975 to 2005) Trends in the Incidence Rates, Clinical Features, Treatment Practices, and Short-Term Outcomes of Patients <55 Years of Age Hospitalized With an Initial Acute Myocardial Infarction

Sparse data are available describing recent trends in the magnitude, clinical features, treatment practices, and outcomes of comparatively young adults hospitalized with acute myocardial infarction (AMI). The objectives of this population-based study were to describe 3 decade-long trends (1975 to 2005) in these end points in adults <55 years old who were hospitalized with an initial AMI. The study population consisted of 1,703 residents of the Worcester (Massachusetts) metropolitan area 25 to 54 years of age who were hospitalized with initial AMIs at all central Massachusetts medical centers during 15 annual periods from 1975 through 2005. Overall hospital incidence rate (per 100,000 residents) of initial AMI in our study population was 66 (95% confidence interval 63 to 69) and incidence rates of AMI decreased inconsistently over time. Patients hospitalized during the most recent study years were more likely to have important cardiovascular risk factors and co-morbidities present but were less likely to have developed heart failure during their index hospitalization. In-hospital and 30-day death rates decreased by approximately 50% (p = 0.04) during the years under study concomitant with increasing use of effective cardiac therapies. In conclusion, the results of this community-wide investigation provide insights into the magnitude, changing characteristics, and short-term outcomes of comparatively young patients hospitalized with a first AMI. Decreasing odds of developing or dying from an initial AMI during the 30 years under study likely reflect increased primary and secondary prevention and treatment efforts.

Heparin-Induced Thrombocytopenia: Patient Profiles and Clinical Manifestations

Despite widespread use of unfractionated heparin for a variety of thrombotic disorders, the frequency of heparin induced thrombocytopenia (HIT) is underappreciated by many clinicians. This can have devastating consequences as this syndrome is frequently associated with limb and life threatening thrombotic events. While the development of novel anticoagulants such as hirudin marks a turning point in the treatment of this disorder, their potential bene®t will not be realized until clinicians are better trained to recognize patients at risk, monitor for a delayed thrombocytopenic reaction to heparin, and identify clinical manifestations of HIT once it occurs.

Platelets: Structure, Function, and Their Fundamental Contribution to Hemostasis and Pathologic Thrombosis

Platelets play a critical role in normal hemostasis by stopping blood loss after vascular injury. By adhering to sites of injury, recruiting other platelets and blood cells to the developing clot, and activating the plasma coagulation cascade, primary hemostasis is effected. In synchrony with the end products of the coagulation cascade, predominantly crosslinked fibrin, a more stable clot quickly forms. However, by these same mechanisms, platelets also contribute directly to pathologic vascular thrombosis. In the ongoing search for means to prevent or temper vascular thrombosis while preserving physiologic hemostasis, a better understanding of platelet structure and function is of paramount importance. In this chapter we provide a composite overview of platelets, focusing on their structure, function, and fundamental contribution to normal hemostasis and pathologic thrombosis.

Factors Associated with Adverse Outcomes in Outpatients Presenting with Pulmonary Embolism: The Worcester VTE Study

Background— Data from clinical trials suggest that short-term mortality in outpatients presenting with pulmonary embolism (PE) is low and that outpatient therapy may be appropriate. However, subjects enrolled in these studies may not be representative of patients seen in the community setting. Methods and Results— The medical records of residents from Worcester, Mass, with International Classification of Disease, Ninth Edition, codes consistent with potential venous thromboembolism during 1999, 2001, and 2003 were independently validated and reviewed by trained abstractors. A total of 305 patients presented with PE from the outpatient setting. The rates of recurrent PE, major bleeding, mortality, or occurrence of any 1 of these end points at 90 days were 1.4%, 9.5%, 11.1%, and 20.1%, respectively. Patients with a history of congestive heart failure, recent intensive care unit discharge, cancer, severe infection, systolic blood pressure <100 mm Hg, and male sex were at increased risk for the composite end point. Conclusions— In the present population-based study, morbidity and mortality after outpatient PE were much higher than what was observed in clinical studies. Our findings raise questions about broad-based outpatient treatment of PE in the community setting. In our study, comorbid conditions and recent illness were important determinants of adverse outcomes, suggesting that these variables should be carefully considered before embarking on outpatient therapy of PE.

Biochemistry of Intra Vascular Clotting: Focus on the Prothrombinase Complex

The prothrombinase complex plays a pivotal role in the coagulation cascade. It is responsible for the proteolytic conversion of prothrombin to thrombin, which in turn is involved directly in the formation of fibrin, activation of platelets, and feedback activation of other components of the cascade. It is among the most thoroughly studied coagulation processes, and some have suggested that the mechanisms of prothrombinase assembly can serve as a model for understanding other components of the coagulation system. Prothrombinase assembly requires a platelet surface in vivo; thus, this stage of clotting involves a unique interaction between the protein-based coagulation cascade and platelet activity. Accordingly, the investigation and development of antithrombotic compounds has recently been directed toward prothrombinase. In this chapter we summarize the current understanding of prothrombinase assembly and function.