Professor of Epidemiology
Associate Professor of Medicine, Harvard Medical School
Dr. Mittleman’s research group at the Institute for Prevention of Cardiovascular Disease is actively involved in research into both the primary and secondary prevention of acute cardiovascular events. His group is actively pursuing 3 lines of research related to the prevention of cardiovascular disease. This research includes: 1. Studies of triggers of acute cardiovascular events, 2. Studies of clinical and behavioral determinants of prognosis following acute myocardial infarction, and 3. Studies of the determinants and prognosis of premature acute coronary syndromes in women. In addition to the work in preventive cardiology, Dr. Mittleman is an expert in epidemiologic methods and is one of the codevelopers of the case-crossover study design. His research interests span the application of this methodology to disciplines other than cardiovascular disease.
Triggers of acute cardiovascular events
In an ongoing series of studies, Dr. Mittleman’s group is investigating the role of physical, psychological and chemical stressors as triggers of acute cardiovascular events, including nonfatal myocardial infarction, ventricular arrhythmias and stroke. The long-term goal of this line of research is to develop a better understanding of the mechanisms through which acute cardiovascular events are triggered, in the hopes of identifying novel preventive strategies.
This work has shown the importance of regular exercise as a means to prevent the onset of myocardial infarction (1) and sudden cardiac death (2) triggered by unusual strenuous activity. In addition, the role of psychological stress, including anger and anxiety, (3,4) have been documented to rarely trigger the onset of acute myocardial infarction. More recently, chemical stressors, including the use of illicit drugs such as cocaine (5) and marijuana (6), have been documented as triggers of acute myocardial infarction. In a recent series of studies, Dr. Mittleman’s group has evaluated the role of particulate air pollution on the onset of cardiovascular events (7). This novel line of research has implications for the public health consequences of current environmental standards set by the Environmental Protection Agency, which are currently under review.
Clinical and behavioral determinants of prognosis following acute myocardial infarction
In a second line of research, Dr. Mittleman’s group has evaluated the role of clinical and behavioral factors on the long-term prognosis of patients hospitalized with acute myocardial infarction. In a study of close to 2000 patients with acute myocardial infarction who were followed for up to 5 years, Dr. Mittleman’s group has evaluated the role of classical clinical features, such as diabetes (8) and gender differences (9) on the risk of dying following acute myocardial infarction. In addition, this research has demonstrated that patients who drink moderate amounts of alcohol (10) or caffeinated tea (11) have a better long-term prognosis with a lower risk of death than patients who do not engage in these behaviors.
Premature acute coronary syndromes in women
For the past 8 years, Dr. Mittleman’s group has been collaborating with investigators at the Karolinska Institute in Stockholm. This research involves an ongoing study of the determinants and prognosis of coronary artery disease in women under age 60. This line of research has led to valuable information regarding the role of biologic markers, including lipoprotein (a) (12), fibrinogen , factor VII, von Willebrand factor, PAI-1 activity (13) on the incidence of acute coronary syndromes in young women. In addition, this study has led to valuable information on psychosocial determinants of coronary artery disease and its prognosis. For example, in a paper published in JAMA 2000, the role of marital stress on the prognosis of women with coronary artery disease was presented (14). Most recently, this collaborative project has led to the collection of serial quantitative coronary angiographies in a group of approximately 100 women who sustained an acute coronary syndrome. Quantitative coronary angiography was obtained at baseline, 3-6 months following the acute event, and repeated approximately 3 years later. A series of studies is currently underway to evaluate clinical characteristics, biomarkers and behavioral factors on progression of atherosclerosis as measured by quantitative coronary angiography in this population. Preliminary results have shown protective effects of moderate alcohol consumption and HDL levels, while high levels of triglycerides and marital stress are independently associated with progression of atherosclerosis.
Studies in Occupational Injury
In addition to the work in preventive cardiology, Dr. Mittleman is an expert in epidemiologic methods and is one of the codevelopers of the case-crossover study design. His research interests span the application of this methodology to disciplines other than cardiovascular disease. In particular, his Dr. Mittleman is the Principal Investigator on two studies of acute traumatic injury in the workplace. In one study, funded by NIOSH, Dr. Mittleman’s group interviewed over 1,100 patients with acute traumatic injury to the hands in a variety of industrial sectors and evaluated the role of transient risk factors in the workplace (16-18). In another study, Dr. Mittleman is investigating the determinants of sharps-related injuries in healthcare workers in a multicenter NIOSH-funded study (19, 20).
1. Mittleman MA, Maclure M, Tofler GH, Sherwood JB, Goldberg RJ, Muller JE for the Determinants of Myocardial Infarction Onset Study Investigators. Triggering of acute myocardial infarction by heavy physical exertion: Protection by regular exertion. N Engl J Med 1993;329:1677-83.
2. Albert C, Mittleman MA, Chae C, Lee I-M, Hennekens CH, Manson JE. Triggering of Sudden Death From Cardiac Causes By Vigorous Exertion. N Engl J Med 2000;343:1355-61.
3. Mittleman MA, Maclure M, Sherwood JB, Mulry RP, Tofler GH, Jacobs SC, Friedman R, Benson H, Muller JE. Triggering of myocardial infarction onset by episodes of anger. Circulation 1995; 92:1720-5.
4. Mittleman MA, Maclure M, Nachnani M, Sherwood JB, Muller JE. Educational attainment, anger and the risk of triggering myocardial infarction onset. Arch Intern Med 1997;157:769?75.
5. Mittleman MA, Mintzer D, Maclure M, Tofler GH, Sherwood JB, Muller JE. Triggering of myocardial infarction by cocaine. Circulation 1999;99:2737-41.
6. Mittleman MA, Lewis R, Maclure M, Sherwood JB, Muller JE. Triggering of myocardial infarction by marijuana. Circulation 2001;103:2805-2809.
7. Peters A, Dockery DW, Muller JE, Mittleman MA. Increased particulate air pollution and the triggering of myocardial infarction. Circulation 2001;103:2810-2815.
8. Mukamal KJ, Nesto RW, Cohen MC, Muller JE, Maclure M, Sherwood JB, Mittleman MA. Impact of diabetes on long-term survival following acute myocardial infarction: Comparability of risk with prior myocardial infarction. Diabetes Care 2001;24:1422-1427.
9. Mukamal KJ, Muller JE, Maclure M, Sherwood JB, Mittleman MA. Evaluation of sex-related differences in survival after hospitalization for acute myocardial infarction. Am J Cardiol 2001;88:768-771.
10. Mukamal KJ, Maclure M, Muller JE, Sherwood JB, Mittleman MA. Prior alcohol consumption and mortality following acute myocardial infarction. JAMA 2001;285:1965-1970.
11. Mukamal KJ, Maclure M, Muller JE, Sherwood, JB, Mittleman MA. Tea Consumption and Mortality Following Acute Myocardial Infarction. Circulation 2002;105:2476-81.
12. Orth-Gomér K, Mittleman MA, Schenck-Gustafson K, Eriksson M, Wamala SP, Belkic K, Kirkeeide R, Svane B, Rydén L. Lipoprotein(a) as a determinant of coronary heart disease in younger women. Circulation 1997;95:329-34.
13. Eriksson M, Egberg N, Wamala S, Orth-Gomér K, Mittleman MA, Schenk-Gustafsson K. Relationship between plasma fibrinogen and coronary heart disease in women. Arterioscler Thromb Vasc Biol 1999;19:67-72.
14. Orth-Gomer K, Wamala S, Horsten M, Schenck-Gustafsson K, Schneiderman N, Mittleman MA. Marital stress worsens prognosis in women with coronary heart disease. JAMA 2000;284:3008-3014.
15. Mittleman MA, Maldonado G, Gerberich SG, Smith GS, Sorock GS. Alternative approaches to analytical designs in occupational epidemiology. Amer J Ind Med 1997;32:129-141.
16. Sorock G, Lombardi D, Hauser R, Eisen E, Herrick B, Mittleman MA. A Case-Crossover Study of Occupational Traumatic Hand Injury: Methods and Initial Findings. Am J Indus Med 2001;39:171-179.
17. Sorock GS, Lombardi DA, Hauser RB, Eisen EA, Herrick RF, Mittleman MA. Acute traumatic occupational hand injuries: Type, location and severity. J Occup Environ Med 2002;44:345-351.
18. Lombardi DA, Sorock GS, Lesch MF, Hauser R, Eisen E, Herrick RF, Mittleman MA. A reliability study of potential risk factors for acute traumatic occupational hand injuries. Amer J Indus Med 2002; (in press).
19. Fisman DN, Mittleman MA, Sorock GS, Harris AD. Willingness to pay in order to avoid sharps-related injuries: a study in injured healthcare workers. Am J Infect Control 2002;30(5):283-7 .
20. Fisman, DN, Harris AD, Sorock GS, Mittleman MA. Sharps-related injuries in health care workers: a case-crossover study. Am J Med 2003;114:688-94.
MDCM, 1985, McGill University
MPH, 1990, Harvard School of Public Health
DrPH, 1994, Harvard School of Public Health