1. Temperature variation and increased mortality in patients with acute myocardial infarction

    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.

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  2. Seasonal Variations in Mortality After Acute Myocardial Infarction.

    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.

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  3. Elderly Subjects and Higher Frequency of Hospitalization for MI in December

    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]

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