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Evidence-Based Therapies and Mortality in Patients Hospitalized in December with Acute Myocardial Infarction

Trip J. Meine, MD; Manesh R. Patel, MD; Venita DePuy, MStat; Lesley H. Curtis, PhD; Sunil V. Rao, MD; Bernard J. Gersh, MB, ChB, DPhil; Kevin A. Schulman, MD; and James G. Jollis, MD
[+] Article and Author Information

From Duke University Medical Center, Durham, North Carolina; and Mayo Clinic, Rochester, Minnesota.


Note: This study was presented in poster form at the American College of Cardiology 53rd Annual Scientific Session, New Orleans, Louisiana, March 2004.

Disclaimer: The contents of this article do not necessarily reflect the views of the Department of Health and Human Services, nor does the mention of trade names, commercial products, or organizations imply endorsement by the U.S. government. The authors assume full responsibility for the accuracy and completeness of the ideas presented. This article is a direct result of the Health Care Quality Improvement Program initiated by the Health Care Financing Administration, which has encouraged identification of quality improvement projects derived from analysis of patterns of care.

Acknowledgments: The authors thank Damon Seils for editorial assistance and manuscript preparation. Data were provided by the Delmarva Foundation for Medical Care, Inc., and the Centers for Medicare & Medicaid Services, both in Baltimore, Maryland.

Grant Support: None.

Potential Financial Conflicts of Interest: None disclosed.

Requests for Single Reprints: Trip J. Meine, MD, 877-B West Faris Road, Greenville, SC 29605.

Current Author Addresses: Drs. Meine, Patel, Curtis, Rao, Schulman, and Jollis and Ms. DePuy: Duke Clinical Research Institute, PO Box 17969, Durham, NC 27715.

Dr. Gersh: Mayo Clinic, Cardiovascular Division, 200 First Street SW, Rochester, MN 55905.

Author Contributions: Conception and design: T.J. Meine, M.R. Patel, S.V. Rao, K.A. Schulman, J.G. Jollis.

Analysis and interpretation of the data: T.J. Meine, M.R. Patel, V. DePuy, L.H. Curtis, S.V. Rao, K.A. Schulman, J.G. Jollis.

Drafting of the article: T.J. Meine, M.R. Patel, B.J. Gersh.

Critical revision of the article for important intellectual content: T.J. Meine, M.R. Patel, V. DePuy, L.H. Curtis, S.V. Rao, B.J. Gersh, K.A. Schulman, J.G. Jollis.

Final approval of the article: T.J. Meine, M.R. Patel, L.H. Curtis, S.V. Rao, B.J. Gersh, K.A. Schulman, J.G. Jollis.

Provision of study materials or patients: L.H. Curtis, S.V. Rao, K.A. Schulman.

Statistical expertise: V. DePuy, L.H. Curtis, J.G. Jollis.

Obtaining of funding: J.G. Jollis.

Administrative, technical, or logistic support: M.R. Patel, L.H. Curtis, K.A. Schulman.

Collection and assembly of data: J.G. Jollis.


Ann Intern Med. 2005;143(7):481-485. doi:10.7326/0003-4819-143-7-200510040-00006
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The study involved 127 959 Medicare beneficiaries. Table 1 gives baseline characteristics of patients hospitalized in December and patients hospitalized during the rest of the year. Although patients hospitalized in December were older, the 2 groups were similar in sex, socioeconomic status, history of hypertension, systolic blood pressure at admission, and rates of anterior infarctions. Table 1 also shows hospital and physician characteristics. Patients hospitalized in December were as likely as other patients to be cared for by board-certified physicians, were more likely to be cared for by an internist, and were more likely to be admitted to a teaching hospital. However, patients hospitalized in December were less likely than other patients to be admitted to a hospital with cardiac catheterization facilities or to be cared for by a cardiologist.

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Elderly Subjects and Higher Frequency of Hospitalization for MI in December
Posted on October 9, 2005
Roberto Manfredini
Vascular Diseases Center, University of Ferrara, Italy
Conflict of Interest: None Declared

We read with interest the paper by Dr Meine et al. (1), reporting a thirty-day mortality rate higher for patients hospitalized with myocardial infarction (MI) in December compared with other months of the year, with no statistical differences in the use of evidence-based therapies.

In addition to MI, a winter preference has been reported for several other cardiovascolar diseases as well, eg, sudden death (2), stroke (3), pulmonary thromboembolism (4), and aortic dissection (5). Moreover, heart failure hospitalization and death have been reported to be higher in winter too (6).

In the study by Dr Meine et al, the main differing characteristic between patients hospitalized in December or in other months of the year was the mean age, that was higher for December admissions. In a recent seven-year study from our group on 4,014 consecutive hospital admission of patients with MI (7), the peak number (9.44%) occurred in the month of December, as well. Interestingly, the inferential chronobiologic analysis, performed with the aim of investigating a possible rhythmicity, showed that only patients aged > 65 years (but not younger subjects) displayed a seasonal pattern of MI, both fatal and non-fatal.

We quite agree with the authors' conclusion that it is unlikely that the increased incidence of MI in winter may be explained by climate- related factors alone. In fact, recent data from the International Registry of Aortic Dissection (IRAD), that endorse multiple centers around the world, have showed that the winter peak in aortic dissection is independent of any geographical variation (8). Probably, a series of clustering external factors, eg, changes in arterial blood pressure, coagulation parameters, acute phase proteins and lipids, as well as some genetically determined endogenous factors, may play a triggering role (7). Further research is needed to investigate the mechanisms of increased cardiovascular mortality in winter, especially for elderly subjects.

1) Meine TJ, Patel MR, DePuy V, Curtis LH, Rao SV, Gersh BJ, et al. Evidence-based therapies and mortality in patients hospitalized in December with acute myocardial infarction. Ann Intern Med. 2005;143:481-5. [PMID: 16204160]

2) Arntz HR, Willich SN, Schreiber C, Bruggemann T, Stern R, Schultheiss HP. Diurnal, weekly, and seasonal variation of sudden death. Population-based analysis of 24,061 consecutive cases. Eur Heart J. 2000;21:315-20. [PMID: 10653679]

3) Gallerani M, Manfredini R, Ricci L, Cocurullo A, Goldoni C, Bigoni M, et al. Chronobiological aspects of acute cerebrovascular diseases. Acta Neurol Scand. 1993;87:482-7. [PMID: 8356879]

4) Gallerani M, Manfredini R, Ricci L, Grandi E, Cappato R, Calò G, et al. Sudden death from pulmonary thromboembolism: chronobiological aspects. Eur Heart J. 1992;13:661-5. [PMID: 1618210]

5) Mehta RH, Manfredini R, Hassan F, Sechtem U, Bossone E, Oh JK, et al. Chronobiological patterns of acute aortic dissection. Circulation 2002;106;1110-5. [PMID: 12196337]

6) Boulay F, Berthier F, Sisteron O, Gendreike Y, Gibelin P. Seasonal variation in chronic heart failure hospitalizations and mortality in France. Circulation 1999;100:280-6. [PMID: 10411853]

7)Manfredini R, Boari B, Smolensky MH, Salmi R, Gallerani M, Guerzoni F, et al. Seasonal variation in onset of myocardial infarction. A 7-year single-center study in Italy. Chronobiol Int 2005;22(6):in press.

8) Mehta R, Manfredini R, Bossone E, Fattori R, Evangelista A, et al. The winter peak in the occurrence of acute aortic dissection is independent of the climate. Chronobiol Int 2005; 22:723-9. [PMID: 16147902]

Conflict of Interest:

None declared

Seasonal Variations in Mortality After Acute Myocardial Infarction.
Posted on October 10, 2005
Alberto Dominguez-Rodriguez
Department of Cardiology. CCU. Hospital Universitario de Canarias. University of La Laguna.
Conflict of Interest: None Declared

TO THE EDITOR: We read with great interest the retrospective study by Meine TJ et al (1), entitled "˜Evidence-based therapies and mortality in patients hospitalized in december with acute myocardial infarction'. The authors should be congratulated for this well-conducted study. However, we would like to point out an important aspect in the interpretation of these findings.

It seems clear that mortality from cardiovascular events, such as acute myocardial infarction, is higher in winter (2). Data from several studies have focused on the seasonal impact on cardiovascular mortality. The study of Sheth et al (3) merited an editorial (4) in the journal Circulation in which it was suggested that the increase of mortality from cardiovascular events in winter might be due to alterations in the biological clocks located in the suprachiasmatic nucleus. Its rhythm is determined by day-night alternation, that is, by light/darkness cycles. These cycles regulate functions such as the secretion of cortisol, blood pressure, vasomotor tone, tissue plasminogen activator, proinflammatory cytokines, etc (5). It might be that, instead of winter cold, the reduction of the number of hours of solar light in winter modulates these pathophysiological processes related to the increase in mortality.

This modulation, via the autonomic nervous system, hormone release, and a variety of other possible pathways, offers a potential mechanism by which the chronobiological rhythms, controlled by the suprachiasmatic nucleus, could affect cardiovascular events, including sudden and nonsudden death, on a daily, weekly, or yearly basis.

References. 1. Meine TJ, Patel MR, DePuy V, Curtis LH, Rao SV, Gersh BJ, et al. Evidence-based therapies and mortality in patients hospitalized in december with acute myocardial infarction. Ann Interm Med. 2005;143:481-5 2. Kloner RA, Poole WK, Perritt RL. When throughout the year is coronary death most likely to occur? A 12-year population-based analysis of more than 220 000 cases. Circulation. 1999;100:1630-4. 3. Sheth T, Nair C, Muller J, Yusuf S. Increased winter mortality from acute myocardial infarction and stroke: the effect of age. J Am Coll Cardiol. 1999;33:1916-9. 4. Zipes DP. Warning: the shorts days of winter may be hazardous to your health. Circulation. 1999;100:1590-2. 5. Gonzalez Hernandez E, Cabades 0'Callaghan A, Cebrian Domenech J, Lopez Merino V, Sanjuan Manez R, Echanove Errazti I, et al. Seasonal variations in admissions for acute myocardial infarction. The PRIMVAC study. Rev Esp Cardiol. 2004;57:12-9.

Conflict of Interest:

None declared

Temperature variation and increased mortality in patients with acute myocardial infarction
Posted on November 3, 2005
PD Kumar
Port Huron Hospital
Conflict of Interest: None Declared

Meine et al 1 report that the increased mortality in hospitalized patients with acute myocardial infarction observed during the month of December is not related to skewed usage of evidence based therapies. This higher incidence could be due to the relative temperature fluctuation observed during winter across the nation. The degree of variation may be more important than the actual temperatures. Figure 1 shows that in all the "˜4 corners' of the country (Boston, Los Angeles, Miami and Seattle) the lowest average temperatures are noted during December and January.2 Various theories proposed to explain this increased incidence of myocardial infarctions and vascular events during the winter months include natural fluctuations in endothelial function, cytokine biology, and adhesion molecules 3 and seasonal changes in platelets, fibrinogen and factor VII .4 Epicardial coronary artery dysfunction assessed by the cold pressor test is found to be predictive of long-term cardiovascular events in hypertensive patients with angiographically normal coronary arteries and without other major coronary risk factors.5 Temperature variation induced changes in the endothelium might predispose to increased coronary events and mortality during the colder months.

References: 1. Meine TJ, Patel MR, DePuy V et al. Evidence-based therapies and mortality in patients hospitalized in December with acute myocardial infarction. Ann Intern Med. 20054;143:481-5. 2. http://www.cityrating.com/ accessed October 12, 2005. 3. Strike PC, Steptoe A. New insights into the mechanisms of temporal variation in the incidence of acute coronary syndromes. Clin Cardiol. 2003;26:495-9. 4. Crawford VL, McNerlan SE, Stout RW. Seasonal changes in platelets, fibrinogen and factor VII in elderly people. Age Ageing. 2003;32:661-5. 5. Nitenberg A, Chemla D, Antony I. Epicardial coronary artery constriction to cold pressor test is predictive of cardiovascular events in hypertensive patients with angiographically normal coronary arteries and without other major coronary risk factor. Atherosclerosis. 2004;173:115-23.

Conflict of Interest:

None declared

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Summary for Patients

Care and Outcomes of Patients Hospitalized with Heart Attack in December

The summary below is from the full report titled “Evidence-Based Therapies and Mortality in Patients Hospitalized in December with Acute Myocardial Infarction.” It is in the 4 October 2005 issue of Annals of Internal Medicine (volume 143, pages 481-485). The authors are T.J. Meine, M.R. Patel, V. DePuy, L.H. Curtis, S.V. Rao, B.J. Gersh, K.A. Schulman, and J.G. Jollis.

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