SUMMARY. Acute myocardial infarction (AMI) was rare a century ago and was diagnosed in few living patients prior to 1925. By 1950, it was the most common heart problem seen by clinicians. Thought at first to have been overlooked, there were many explanations offered for its neglect.
Smoking, hypertension, and elevated cholesterol are associated with AMI, but of these only smoking should be considered a cause. Hypertension and hypercholesterolemia may be co-effects, perhaps of inflammation stimulated in the lung and blood vessels by smoking and air pollution, thus affecting vessels and arteries subjected to systemic blood pressure. Air pollution--the 20th century's other "big smoke"--deserves consideration as a 2nd cause.
Auto exhaust blankets the world's cities. It consists of smoke and other effluents of petroleum vaporization and combustion that emanate from the crankcases and exhaust pipes of trucks and automobiles. The major living spaces (conurbations) of the world now imitate and exceed Los Angeles in their levels of air pollution. Auto exhaust gases fit the timeline, and their increasing amounts parallel the worldwide rise in coronary heart disease. Increasing doses of these chemicals imitate cigarette smoke and stimulate inflammation in the lungs. They appear to be absorbed into the blood, where they cause inflammation in blood vessels, increased blood pressure, and clogged coronary arteries.
Avoidance is the obvious solution. Quit inhaling cigarette smoke and motor vehicle exhaust. The benefits have been shown and can be proved by intervention. The quest for clean air is hygienic--like avoiding water contaminated with feces was 150 yr ago. Clear air must be made a moral right. Its attainment requires a major revolution in priorities for energy use and lifestyle. Two types of smoke must be avoided.
The world's most lethal disease. In 1876, Adam Hammer described a 34-yr-old man who collapsed without pain and whose pulse rate decreased incrementally from 40 to 16 beats per minute. (1) Hammer reasoned that this event was caused by a thrombotic occlusion of a coronary artery. A thrombus in the right sinus of Valsalva was confirmed at autopsy. In 1882, Karl Huber reported on 17 patients with cardiac infarcts, which he attributed to occluded coronary arteries. (2) Sir William Osier described infarction of the heart's papillary muscle in 1892. (3)
Coronary heart disease/acute myocardial infarction (CHD-AMI) kills 6,300,000 people in the world each year; 3.5 million fatal heart attacks occurred in developing countries in 1999. (4,5) CHD-AMI was an exotic curiosity in the 19th century. However, many patients were diagnosed in the 1st quarter of the 20th century, and by the 1950s (6) CHD-AMI was a major cause of death in the United States and Britain. The epidemic raged through Europe, and by 1990 it had circled the globe. The increase in CHD-AMI was associated with widespread cigarette smoking and a mammoth increase in the burning of gasoline and diesel fuel. Combustion for transportation marked cities worldwide. Given that there has been a weighting of these associations and other co-temporal trends, one must ask: Why have the causes of CHD-AMI eluded us for 50 yr? A new perspective is needed. I suggest we think in terms of chemical causes for CHD-AMI.
A 20th century epidemic. No one seems to have suggested what seems obvious now--that the epidemic of coronary artery obstruction and AMI was new in the 20th century. Hammer's and other thoughtful clinicians' investigations had anticipated its origins in the mid-19th century. Among the first was Marshall Hall who, in 1842, delivered his Gulstonian lecture on coronary circulation: "Sudden Death, a Clinico-Pathological Correlation." (7) Also in 1842, John Ericksen placed ligatures around the coronary arteries of dogs and rabbits and found that when he tied them quickly the animals' hearts stopped. (7) By 1887, Cohnheim repeated these experiments and showed that, after 30-40 sec, the pulse became intermittent, and after 105 sec the ventricles quit beating, (7) thus providing experimental confirmation of the sequence in Hammer's patient.
Pathologists Cruveilhier in 1842, Rokitansky in 1856, and later Virchow, described infarcts of the heart. (7) In 1863, Boettger, an asylum physician, reported 62 instances of heart rupture, usually accompanied by sudden death, although sometimes patients survived for 18 hours. (7,8)
In the new century, discovery quickened its pace, and by 1910 Osier, (9) in his Lumleian lectures on angina pectoris, described a patient whose left coronary artery was blocked by a thrombus and whose left ventricular wall was perforated. Seventeen of his patients had fatal angina confirmed by autopsy examinations. That year also, Obrastzow and Straschesko reported 3 patients from Kiev with coronary obstruction, (10) and in 1911, Hochhaus diagnosed coronary occlusion in 4 patients from Cologne. (11)
Diagnosis in a living patient. In 1912, James Herrick, a St. Louis physician, was 1st to recognize a myocardial infarction in a living patient. (8) Thirty years later, Herrick lamented in his short history of cardiology (7) that clinicians showed "dogged slowness" in diagnosing myocardial infarction. This was expressed despite a virtual flood of papers on the subject in the late 1930s from the United States, Britain, Europe, and South America. Herrick highlighted Bedford's (12) observation from Great Britain in 1933--that knowledge of this disease originated largely in the preceding 20 yr from Americans (who were also smoking many more cigarettes than were individuals from Great Britain). Cigarette advertising became a factor in 1913, when it targeted women with the advice to reach for a smoke instead of a "sweet." Subsequently, AMI mushroomed to become the world's leading cause of death by 1990.
Herrick followed his 1st report with another in 1919. (13) Joseph Wearn (14) amplified the description with information on 10 patients diagnosed in Boston by the newly developed electrocardiogram in 1923; all of the patients eventually died. Thus, coronary thrombosis, with heart damage determined by electrocardiogram, was correlated with death from myocardial infarction. Thereafter, the disorder emerged like lightning, with the result that 100 patients from Britain were reported in 1928. In addition, in 1929 Samuel Levine published the first book about the disorder, as determined in 145 Boston patients. (15)
Therapy but not causation. Clinical care emphasized strict bed rest for 6 wk, and supportive care. Observation of the debilitating effects of bed rest led to the bed/chair regime, followed by early ambulation. (15) Progressively, improvements in care came to include quick triage to coronary intensive care units, early coronary catheterization, and angiography. Surgical revascularizing of the heart to bypass coronary obstructions followed, as did catheter angioplasty and fibrinolytic drugs. Other drugs reduced blood pressure, slowed blood clotting, and restored heart rhythm.
Why did awareness lag knowledge? George Dock (9) observed in 1939 that "severe angina and infarction were less frequent prior to 1910 than at the current time, as was certainly the case in hospitals." In his opinion, the role of the coronary arteries in pathologic states of the heart was understood 50 yr earlier, and he thought that the "facts were not quickly and widely diffused." Dock had worked with several of the 19th century's great physicians from 1884 to 1887, including Virchow, Huber, Weigart, Leyden, and Osier. Dock attributed the neglect of myocardial infarction to many infectious disease novelties that were presented concurrently to the medical community. Among those were the "causes of sepsis, tuberculosis, typhoid, diphtheria, malaria, pneumonia, and meningitis--together with the concepts of antisepsis and asepsis."
In 1942, Herrick--30 yr after his first diagnosis--posited additional reasons for the delay in awareness. (7) First, heart fibrosis was considered an inflammatory process by Rokitansky and Virchow. Second, Cohnheim, Hall, and Ericksen thought that deaths from coronary ligation in experimental animals were "not of interest for clinicians." Third, auscultation dominated the diagnosis of heart disease; the heart was thought to be intact if its sounds were normal. Fourth, a veil of obscure terms (Herrick termed them captions), including angina pectoris, cardiac neuroses, infarct of the myocardium, myocarditis, aneurysm, and pericarditis, splintered the problem so that no one viewed the heart's "big picture." Herrick endorsed Dock's suggestion that attention had been diverted by many new ideas hitting doctors all at once. (9)
Advances in diagnostic technology. Herrick listed 3 technological advances that helped in the diagnosis of myocardial infarction: Mackenzie's polygraph, Roentgen's x-ray, and Einthoven's electrocardiograph. The latter was made clinically useful by Lewis's ground lead and 6 precordial recording sites. Bruce Fye, who summarized this history in 1985 (16) and again in 1991, (17) could not explain why the modern coronary heart disease epidemic was not recognized earlier.
Role of hypertension. Hypertension was braided into the rope of AMI, (18) beginning with Richard Bright who, in 1827, described fatal kidney failure (albuminuria), an enlarged heart, and edema--all of which led to anasarca--in a 55-yr-old patient. (19) The man's heart was greatly thickened on the left side, and the kidneys were small and hard--nearly cartilaginous--with granulated surfaces, which define the pathological findings of hypertensive heart disease. In 1872, Gull and Sutton (20) observed by microscopy the thickening of the kidney's minute arteries and capillaries by a hyaline-fibroid substance. In 1913, Theodore Janeway measured high blood pressure by sphygmomanometry, thus applying a 4th technology--but hypertension was nonetheless diagnosed clinically. (21)
Paul White, writing from his Boston private practice in 1936, (22) found that, in 22% of 5,808 patients, hypertension was a precursor to heart disease. And 72 of 100 consecutive cases he had followed in which the victims died before age 70 had hypertrophy of the left ventricle. In 1999, hypertension, which occurred in 50% of individuals after age 60, was labeled "essential," meaning of unknown cause. (23) Thus, hypertension, as described by Bright, contributed to myocardial infarction being acknowledged by 1950.
Acute coronary occlusion and myocardial infarction moved from rare to commonplace by the mid-20th century. Medical care for coronary heart disease currently costs $50 billion per year in the United States alone. Why did myocardial infarctions become widespread? Which of the 20th century's co-temporal phenomena were causal? A "hypothesis seems inevitable." One novel suggestion--a fetal origin (24) related to maleness and prematurity--flies in the face of data on women showing that cigarette smoke is a major cause of their coronary occlusion and myocardial infarction.
Considering causes. William Dock, the son of George Dock, observed in 1946 (25) that 1 of 5 physician deaths reported to the Journal of the American Medical Association resulted from coronary disease--twice the cancer mortality at that time. Dock suggested that the ratios were similar for businessmen, lawyers, clergy, teachers, clerks, and supervisors. This "new" principal cause of death struck at the age at which earning capacity was highest. Elevated cholesterol and hypertension were often associated, and then acknowledged as risk factors. Dock omitted mention of cigarette smoking, which was largely a male habit in 1946.
Cigarette-smoking link begrudged. Evidence that smoking cigarettes harmed the heart emerged slowly, as was noted by Sir Thomas Lewis, Britain's dean of cardiologists. Lewis focused on nicotine in Diseases of the Heart, published in 1933, (26) but he stated that "heavy cigarette smoking led to degeneration of arteries, including the coronaries." He likely had Buerger's (1908) (peripheral) arterial obstructive disease in mind, (27) but he considered the evidence insufficient to attribute excessive cigarette smoking to spasm or obstruction of the coronary arteries.
Twelve years later, Boston cardiologist Samuel Levine--whose 1929 book (15) defined AMI--had 2 notes on tobacco in his 1950 Clinical Heart Disease. (28) First, death from coronary disease occurred 3 yr earlier in cigarette smokers than in nonsmokers, and 2nd, women had coronary disease at older ages than did men. He acknowledged that smoking was a risk factor for AMI, but he considered it less important than cholesterol or syphilis. Another Boston cardiologist, Paul White, in his 1951 book Heart Disease, (29) noted that smoking increased the heart rate and blood pressure and inverted the t-waves in the electrocardiogram--effects that were duplicated by injection of nicotine. He also referenced Buerger and taught that smoking caused peripheral vascular disease, but he did not link smoking and AMI.
Cigarette smoking connected. Cuyler Hammond and Daniel Horn were hunting for clues for cancer in a questionnaire survey of a million Americans in 1954. (6) They observed that men who smoked 20 cigarettes a day had twice the coronary death rate of nonsmokers. Later they found that those who stopped smoking decreased these rates substantially during 12 yr of follow-up--a crucial observation. Doll and Hill confirmed that death rates from coronary disease decreased as British doctors stopped smoking. (30) That cessation of smoking reduces AMI has been confirmed repeatedly, but it has attracted little attention. Smoking effect is usually diluted in the so-called lifestyle factors (e.g., obesity, cholesterol, and lack of exercise). Emphasis on new treatments for myocardial infarction overshadowed evidence of the causal role of smoking. New treatments--"incomplete technologies," to use Lewis Thomas's label (31)--included coronary bypass surgery, angioplasty, and drugs to block calcium channels, control arrhythmias, and lower cholesterol. No one should be misled, however; these treatments, remarkable as they are in relieving pain, have not reduced mortality or addressed the cause of coronary disease. Americans died with less pain--perhaps later than if no treatment was provided--but the decrease in incidence of CHD-AMI since 1970 has occurred among groups who quit smoking.
Risk factors. The agreed risk factors for CHD-AMI are cigarette smoking, hypertension, and elevated serum cholesterol (also encompassing obesity and diabetes mellitus). (32) But only cigarette smoking has the properties and timing of a cause. (4,5) It was reaffirmed as the most powerful factor in the World Health Organization's MONICA study populations. (23)
Cholesterol and diabetes. Cholesterol and low-density lipids have a paradoxical role. Half of patients with CHD-AMI do not have elevated cholesterol levels, (33) suggesting its influence is not decisive for paths to coronary thrombosis. Whether dietary fat influences coronary heart disease is increasingly questioned. (34) The lowering of high serum cholesterol levels has had less impact on CHD-AMI than has cessation of smoking. (33-36)
As many as 75% of deaths in non-insulin-dependent diabetic persons are from CHD-AMI--2 to 5 times the nondiabetic risk. (37,38) The other diabetic vascular disorders are thickening of basement membranes in vessels; microvascular disease of the eye, kidney, and nerves; and macrovascular disease of coronary and cerebral arteries. (37,38) Eight percent of adults in the United States and Europe have diabetes. Diabetes affects 100 million people worldwide, (32) thus representing an increased incidence that parallels the incidence of CHD-AMI.
Reducing the risk factors, other than smoking, for CHD-AMI did not lower the incidence of myocardial infarction from 1987 to 1994, although annual reductions in mortality suggested prolonged survival. (35,39)
Cigarette promotion and national advertising that began in 1913 boosted smoking rates during both world wars and during the intervening depression. (40) CHD-AMI deaths doubled many times as more people smoked. Passive smoke exposure increased CHD-AMI risk 20-70%. (41) The first good news was that deaths decreased dramatically when white males quit smoking. (6,30,36) In addition, physicians in the United States had fewer strokes after they ceased smoking. (42) Recently, data from China showed that 300 million Chinese men smoke; they consume 1/3 of the cigarettes smoked in the world (i.e., 1.8 trillion/yr). In China, 1 man in 8 will die of lung cancer, CHD-AMI, and other smoking-related diseases (43)--an awesome toll.
Perhaps hypertension and elevated cholesterol should be considered co-temporal consequences of smoking, along with CHD-AMI. Hypertension (44) may have additional chemical causes with strikingly parallel upward trends merging into CHD-AMI. (23) Several chemical mixtures may have roles in hypertension that link to air pollution, urbanization, and commuting by automobile. Prime suspects are synthetic chemicals, including carbon disulfide, rayon, trichloroethylene, vinyl chloride, styrene, and polychlorinated biphenyls. (45,46)
Air pollution. The incidence of CHD-AMI, and of lung cancer, escalated in the 20th century as more people inhaled smoke from burning cigarettes and liquid fuels. Air pollution increased many fold as a result of worldwide population growth, industrialization, and automobile transportation. Given the basis of these many upward trends, why are these facts noteworthy? They add a heart tone to the theme of processing inhaled particles. Particles inhaled into the lungs are eaten--phagocytized--by cells. Since 1950, people have inhaled progressively more, by many times, fossil fuel combustion products than before 1920. The burdens of inhaled products of gasoline, and diesel and jet fuels, exceed by many fold those experienced in the coal and kerosene era. (45,46) Air pollution encompasses far more than the familiar total suspended particles, oxidant gases, and sulfur dioxide. Hydrocarbons as gases and solids, and oxidant gases adhere to smoke's minute respirable particles, which include oil droplets. These chemical components stimulate inflammation and repair, thus producing chronic bronchitis and emphysema, and they incite lung cancer. (47) Inflammation's roles in vascular damage continue to be investigated, (48,49) and they appear crucial for CHD-AMI.
Chemical use in America rose 150 times in 40 yr (i.e., from 2 billion pounds in 1950 to 300 billion pounds in 1990). (50) Gasoline and diesel burning increased 5-fold (50) as the numbers of cars increased from 26 million in 1945 to 130 million in 1995. At the same time, chemical wastes were evaporating from more than 1,700 federal Superfund sites, from thousands of similar sites in the 50 states, and from an estimated 450,000 "brown" sites (i.e., chemical-contaminated locations of former industries). (50) In addition, there are airborne fugitive emissions of chemicals from oil refineries and chemical-manufacturing sites.
Smoke's postulated mechanism. Analogy to the undeniable causal role of cigarette smoke in CHD-AMI fuels the hypothesis. Burdens of trillions of particles of combustion from cigarette tobacco and fossil fuel land in the lung and are taken up by scavenger cells (macrophages) or by the endothelial cells of blood vessels, with resulting initiation of inflammation in the coronary and cerebral arteries.
Lacking an escape route from the body, particles forced to reside in the lung stimulate digestive enzymes in macrophages. The liberated enzymes spill into the lung vessels and the general circulation. The lung and body's efforts to digest and dispose of these particles activate 3 inflammatory cascades. One damages the walls of pressure-regulating arteries and arterioles, thus causing hypertension. (38,51) The 2nd attacks vessel walls and produces atheroma, which causes vessels to narrow. (49,51) The 3rd stimulates blood clotting, which obstructs these damaged vessels. (52,53) Obstructed coronary arteries infarct the myocardium; blocked cerebral vessels produce strokes.
Billions upon billions of airborne particles are deposited daily into the lungs of urban dwellers. (47,54) One puff (30 ml) of cigarette smoke contains 70 billion particles. In the Augsburg MONICA survey, suspended particles during an episode of air pollution raised blood pressure, which further increased with rising heart rates and blood viscosity. (44) Healthy human volunteers experienced artery vasoconstriction when they breathed fine particulate air pollution and ozone. (55)
Roles of other chemicals. Arsenic inhaled by copper smelter workers causes cold, blanched fingers. This vasospasm is called Raynaud's phenomena, (56) and it advances to explain epidemics of peripheral necrosis and dry gangrene of fingers and toes from arsenic in drinking water in Taiwan, Tibet, and Peru. (57) Other chemicals trigger vascular disease--as was the case in the toxic oil incident in Spain, in which consumption of aniline-adulterated rapeseed oil produced widespread vascular lesions. Inner (myointimal) layers of heart muscle degenerated with microembolization. (58) Elevated levels of homocysteine in serum are associated with CHD-AMI. (59) Reactive oxygen species associated with air pollutants stimulate vascular smooth-muscle proliferation and impair vasomotor regulation. (55,59,60) Chemicals from cigarette smoke raise blood pressure, most likely by damaging blood vessels in the brain and kidneys.
Naturally occurring interventions: experiments in progress. Individuals who are not exposed to products of diesel and gasoline combustion should have less hypertension, CHD-AMI, and stroke. This was true in rural America before 1950 and in people in rural areas of developing countries. (61-63) Rural Africans who were inducted into the army or who had migrated to cities experienced a rapid increase in blood pressure. (62) Consistent with this effect, heavy exposure to products of hydrocarbon fuel combustion increased vascular diseases, as was observed in tunnel workers in Boston and New York, (64) London, Los Angeles, (65) and, finally, the 50 states. (54)
Epidemiological studies, including interventions, could verify or refute these relationships, presuming "clean" populations exist in the world. Repeating these social experiments would require the same kinds of economic and political changes that were needed to ensure safe water and milk, and to combat infectious diseases after 1850. Venice, Italy, could participate by reducing cigarette smoking because they have no automobiles on the island. Encouragement for executing such experiments should be a top priority of the World Health Organization. I propose that payment should originate from the new worldwide Health Hazard Taxes paid to the World Health Organization from profits originating from "big tobacco" and bigger oil companies. Meanwhile, the beneficial effects of ceasing to smoke cigarettes suggest that (a) all individuals worldwide must stop smoking and (b) there must be a reduction in exposure to combustion products of fossil fuel to cut the costs and avert the fatal complications of vascular diseases. To these ends, I propose that the following crucial steps be taken:
Step 1. The cultivation of tobacco and the manufacture of cigarettes and related products should cease. This would be the most important initiative for health in world history. Raising the price of cigarettes reduces smoking; therefore, higher taxes would help. Several states should call in the debt settlements from tobacco litigation and put out of business the tobacco arms of multinational tobacco, food, and liquor companies. Individuals in the United States must direct their federal government to stop tobacco allotments, end tobacco price supports, and restructure farming in the South for the raising of alternative crops such as soybeans or cotton. The impact of cigarette smoking on cardiovascular disease is huge in developing countries (66); therefore, export of this deadly commodity also must cease.
Step 2. The burning of fossil fuels must be significantly reduced. The practical electrical, hydrogen, and fuel-cell cars that are needed are already being used in road trials. (67-69)
To prevent this deadly disease, we must stop inhaling the 2 types of smoke. Reduction in the inhalation of smoke would save $15 billion currently being spent for 1 million coronary bypass and angioplasty operations each year, with overall costs of more than $51.2 billion per year in the United States alone. (70) The worldwide costs of CHD-AMI could bankrupt nations if they were to provide the level of care expected in the United States.
References
(1.) Hammer A. Ein Fall von Thrombotischem. Verschlusse Einer der Kranzarterien des Herzens. Wien Med Worchenschrift 1878; 28:97-102.
(2.) Huber K. Uber den Einfluss der Kranzarterienerkrantkungen auf das Herz und die Chronische Myocarditis. Virchows Arch Pathol Anat 1882; 89:236-58.
(3.) Osier W. Principles and Practice of Medicine. New York: P. Appleton & Company, 1892.
(4.) Fuster V. Epidemic of cardiovascular disease and stroke: the three main challenges. Circulation 1999; 99:1132-37.
(5.) Horton R. Future of European cardiology: continentally isolated or globally integrated. Lancet 1993; 354:791-92.
(6.) Hammond EC, Horn D. Smoking and death rates: report on forty-four months of follow-up of 187,783 men. II. Death rates by cause. JAMA 1958; 166:1294-1308.
(7.) Herrick JB. A Short History of Cardiology. Springfield, IL: Thomas Books, Charles C. Thomas, 1942.
(8.) Herrick JB. Clinical features of sudden obstruction of the coronary arteries. JAMA 1912; 59:2016-20.
(9.) Dock G. Historical notes on coronary occlusions: from Heberden to Osier. JAMA 1939; 113(7):563-68.
(10.) Obrastzow WP, Straschesko ND. Zur kenntnis der thrombose der koronararterien des herzens. Z Kiln Med 1910; 71:116-32.
(11.) Hochhaus H. Zur diagnose des potzlichen verschlusses der kranzarterien des herzens. Deutsche Med Worchenschrift 1911; 45:2065-68.
(12.) Parkinson J, Bedford DE. Cardiac infarction and coronary thrombosis. Lancet 1928; 211:4-11.
(13.) Herrick JB. Thrombosis of the coronary arteries. JAMA 1919; 72:387-90.
(14.) Wearn JT. Thrombosis of the coronary arteries, with infarction of the heart. Am J Med Sci 1923; 165:250-76.
(15.) Levine SA. Coronary Thrombosis: Its Various Clinical Features. Baltimore, MD: Williams & Wilkins, 1929.
(16.) Fye WB. The delayed diagnosis of myocardial infarction: it took half a century. Circulation 1985; 72(2):262-71.
(17.) Fye WB. Acute Myocardial Infarction: A Historical Summary. In: Gersh BJ, Rahemtola SH (Eds). Current Topics in Cardiology. New York: Elsevier Science Publishing Co., 1991; pp 3-13.
(18.) White PD. The heart in hypertension since the days of Richard Bright. Can Med Assoc J 1946; 54:129-35.
(19.) Bright R. Reports of Medical Cases Selected with a View of Illustrating the Symptoms and Cure of Diseases by a References to Morbid Anatomy. Longman, Reese, Orme, Brown and Green (Eds). London, U.K.: 1827.
(20.) Gull WW, Sutton HG. On the pathology of the morbid state commonly called chronic Bright's Disease. Trans Med Chir Soc 1872; 55:273-77.
(21.) Janeway TC. A clinical study of hypertensive cardiovascular disease. Arch Int Med 1913; 11:755-98.
(22.) White PD. A note on the common occurrence of serious involvement of the heart in hyperpiesia. N Engl J Med 1936; 214:719-24.
(23.) Kuulasmaa K, Tunstall-Pedoe H, Dobson A, et al. Estimation of contribution of changes in classic risk factors to trends in coronary-event rates across the WHO MONICA project populations. Lancet 2000; 355:675-87.
(24.) Barker DJP. Fetal origins of coronary heart disease. BMJ 1995; 311:171-74
(25.) Dock W. The predilection of atherosclerosis for the coronary arteries. JAMA 1946; 131:875-78.
(26.) Lewis T. Diseases of the Heart. London, U.K.: The Macmillian Co., 1922.
(27.) Buerger L. Thromboangiitis obliterans: a study of the vascular lesions leading to presenile spontaneous gangrene. Am J Med Sci 1908; 136:567-80.
(28.) Levine SA. Clinical Heart Disease. Baltimore, MD: Williams & Wilkins, 1950.
(29.) White PD. Heart Diseases. New York: The Macmillian Co., 1951.
(30.) Doll R, Hill AB. The mortality of doctors in relation to their smoking habits. BMJ 1954; 1:1451-55.
(31.) Thomas L. Lives of a Cell: Notes of a Biology Watcher. New York: Viking-Penguin, 1971.
(32.) Taubes G. The soft science of dietary fat. Science 2001; 291:2536-45.
(33.) Fuster V, Vorchheimer DA. Prevention of atherosclerosis in coronary artery bypass grafts. N Engl J Med 1997; 336:212-13.
(34.) Schmidt MI, Duncan BB, Sharrett AR, et al. Markers of inflammation and prediction of diabetes mellitus in adults (atherosclerosis risk in community study): a cohort study. Lancet 1999; 353:1649-52.
(35.) Levy D, Thom TJ. Death rates from coronary disease--progress and a puzzling paradox. N Engl J Med 1998; 339:915-17.
(36.) Burns DM, Shanks TG, Choi W, et al. The American Cancer Society Prevention Study. I. 12-year follow-up of 1 million men and women. In: Shopland DP, Burns DM, Garfinkel L, Samet JM (Eds). Changes in Cigarette-Related Disease Risks and their Implication for Prevention and Control. Smoking and Tobacco Control Monograph 8. Bethesda, MD: National Institute of Health (NIH), National Cancer Institute, NIH Pub. #97-4213; 1997.
(37.) Geiss LS, Herman WH, Smith PJ. Mortality in non-insulin dependent diabetes. In: Harris M (Ed). Diabetes In America. 2nd ed. Bethesda, MD: National Institutes of Health, 1995; pp 233-655.
(38.) Zimmet PZ, Alberti KGMM. The changing face of macrovascular disease in non-insulin dependent diabetes mellitus: an epidemic in progress. Lancet 1997; 350(Suppl 1):1-4.
(39.) Rosamond WD, Chambless LE, Folsom AR, et al. Trends in the incidence of myocardial infarction and in mortality due to coronary heart disease, 1987 to 1994. N Engl J Med 1998; 339:861-67.
(40.) U.S. Department Health and Human Services. The Health Benefits of Smoking Cessation: A Report to the Surgeon General. Washington, DC: Government Printing Office, 1990. [DHHS publication No.(CDC) 90:8416.]
(41.) Wells AJ. Passive smoking as a cause of heart disease. J Am Coil Cardiol 1994; 24:546-54.
(42.) Robbins AS, Manson JE, Lee IM, et al. Cigarette smoking and stroke in a cohort of US male physicians. Ann Intern Med 1994; 120:458-62.
(43.) Chu H. Men in China are literally dying for a cigarette. Los Angeles Times, October 31, 1999.
(44.) Ibald-Mulli A, Stieber J, Wichmann HE, et al. Effects of air pollution on blood pressure: a population-based approach. Am J Public Health 2001; 91:571-77.
(45.) Hottel HC, Howard JB. An Agenda for Energy. Edited at Massachusetts Institute Technology. Technology Review, January 1972.
(46.) Dorf RC. Energy Fact Book. New York: McGraw-Hill, 1981.
(47.) Kilburn KH. Functional morphology of the distal lung. Int Rev Cytol 1974; 37:153-70.
(48.) Ross R. Atherosclerosis--an inflammatory disease. N Engl J Med 1999; 340:115-22.
(49.) Lippy, R Atherosclerosis: the new view. Sci Am 2002; 286:47-55.
(50.) U.S. Environmental Protection Agency Office of Solid Waste and Emergency Response. Dimensions of the Problem: Exposure Assessment. Environmental Epidemiology, Vol. 1. Public Health and Hazardous Wastes. Washington, DC: National Academies Press, 1991; pp 114-16.
(51.) Entman ML, Michael L, Rossen RD, et al. Inflammation in the course of early myocardial ischemia. FASEB J 1991; 5:2529-37.
(52.) Grimm RH Jr, Neaton JD, Ludwig W. Prognostic importance of the white blood cell count for coronary, cancer and all-cause mortality. JAMA 1985; 254:1932-37.
(53.) Ernst E, Hammerschmidt DE, Bagge U, et al. Leukocytes and the risk of ischemic diseases. JAMA 1987; 257(17):2318-24.
(54.) Pope AC, Burnett RT, Thun MJ, et al. Lung cancer, cardiopulmonary mortality and long-term exposure to fine particulate air pollution. JAMA 2002; 287(9):1132-41.
(55.) Brook RD, Brook JR, Urch B, et al. Inhalation of fine particulate air pollution and ozone causes acute arterial vasoconstriction in healthy adults. Circulation 2002; 105:1534-36.
(56.) Lagerkvist B, Linderholm H, Nordberg GF. Vasospastic tendency and Raynaud's phenomenon in smelter workers exposed to arsenic. Environ Res 1986; 39:465-74.
(57.) I-Cheng CHT, Blackwell RQ. A controlled retrospective study of Blackfoot disease: an endemic peripheral gangrene disease in Taiwan. Am J Epidemiol 1968; 88:7-24.
(58.) James TN, Posada-de la Paz M, Abaitua-Borda I, et al. Histologic abnormalities of large and small coronary arteries, neural structures, and the conduction system of the heart found in postmortem studies of individuals dying from the toxic oil syndrome. Am Heart J 1991; 121:803.
(59.) Hankey GJ, Eikelborn JN. Homocysteine and vascular disease. Lancet 1999; 354:407-13.
(60.) Maseri A, Crea KF, Clanflone D. Myocardial ischemia caused by coronary vasoconstriction. Am J Cardiol 1992; 70:1602-05
(61.) Shaper AG, Hutt MSR, Fejfar Z. Communities Without Hypertension. Cardiovascular Disease in the Tropics. London, U.K.: British Medical Association, 1974; pp 77-83.
(62.) Shaper AG. Blood pressure studies in East Africa. In: Stamler J, Stamler R, Pullman TN (Eds). The Epidemiology of Hypertension. New York: Grune & Stratton, 1967; pp 139-49.
(63.) Poulter N, Khaw KT, Hopwood BEC, et al. Blood pressure and its correlates in an African tribe in urban and rural environments. J Epidemiol Community Health 1984; 38:181-86.
(64.) Ayres SM, Evans R, Licht D, et al. Health effects of exposure to high concentrations of automotive emissions. Arch Environ Health 1973; 27:168-78.
(65.) Cohen SI, Deane M, Goldsmith JR. Carbon monoxide and survival from myocardial infarction. Arch Environ Health 1969; 19:510-17.
(66.) Reddy K, Srinath DM, Salim Y. Emerging epidemic of cardiovascular disease in developing countries. Circulation 1998; 97(6):596-601.
(67.) Malakoff D. U.S. supercars: around the corner, or running on empty? Science 1999; 285:680-82.
(68.) Service RF. Bring fuel cells down to earth. Science 1999; 285:682-85.
(69.) Burns LD, McCormick JB, Borroni-Bird CE. Vehicle of change. Sci Am 2002; 287:64-73.
(70.) National Center for Health Statistics. Detailed diagnosis and procedures. National Hospital Discharge Survey, 1993. Vital and Health Statistics, Series 13, No. 122. Washington, DC: U.S. Government Printing Office (DHHS) Pub. No. (PHS) 95-1783; 1995.
Kaye H. Kilburn, M.D.
University of Southern California
Keck School of Medicine
Environmental Sciences Laboratory
2025 Zonal Avenue, CSC 201
Los Angeles, California 90033
E-mail: kilburn@usc.edu
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