Heart

by Sandeep Jauhar

  But as important as the Framingham Heart Study has been in advancing our understanding of coronary heart disease, it does not tell the whole story. For example, Framingham risk models do not seem to apply equally to nonwhite ethnic groups. Meadors and the early Framingham investigators recognized the lack of diversity in the study population as a major limitation.* What of my medical school cadaver or my grandfather? In 1959, the first study showing an increased risk of premature heart disease in Indian males was published in The American Heart Journal. These men had four times the rate of heart disease compared with men living in Framingham, despite having lower rates of hypertension, smoking, and high cholesterol and more often consuming a vegetarian diet. Today in South Asia, a large percentage of heart attacks occur in men with zero or only one Framingham risk factor. Over the past half century, coronary artery disease rates have increased threefold in urban India and twofold in rural India. During that time, the average age at which a first heart attack occurs has increased by ten years in the United States but decreased by about ten years in India. Compared with whites, South Asians have more multivessel coronary artery disease and are more likely to have a more dangerous anterior location of a myocardial infarction. South Asians will soon make up over half of the world’s cardiac patients. What is it about South Asian genetics or environments that leads to so much heart disease? We need a Framingham-type study to answer this question.*

  But there are almost certainly cardiovascular risk factors that Framingham investigators did not identify. Some of these factors are likely in the “psychosocial” domain that Framingham investigators decided to ignore when the study was taken over by the NHI in the early 1950s. For example, consider heart disease in Japanese immigrants. Coronary artery disease is relatively rare in Japan. However, its rate is almost double in Japanese immigrants who settle in Hawaii and triple in those who settle in the mainland United States. Part of the explanation might be that Japanese immigrants adopt unhealthy American habits, like a sedentary lifestyle or a diet rich in processed foods. Still, Framingham risk factors do not fully explain the disparity.

  In the early 1970s, Sir Michael Marmot and his colleagues at the UC Berkeley School of Public Health studied nearly four thousand middle-aged Japanese men living in the San Francisco Bay Area. They found that immigrants who stayed true to their Japanese roots (as evidenced in surveys by their ability to read Japanese, the frequency with which they spoke Japanese, the frequency with which they had Japanese co-workers, and so on) had a much lower prevalence of heart disease, even when they matched Americans in terms of serum cholesterol and blood pressure, than immigrants who were more integrated into their new culture. “Traditional” Japanese immigrants had coronary disease rates in line with their homeland counterparts. “Westernized” immigrants had a prevalence that was at least three times higher. “Retention of Japanese group relationships is associated with a lower rate of coronary heart disease,” the authors concluded. And so, acculturation, they declared, is a major risk factor for coronary disease in immigrant populations.

  If cutting traditional cultural ties increases the risk of heart disease, then psychosocial factors must play a role in cardiovascular health. Today we know this to be true in many strata of human society. For example, American blacks in poor urban centers have a much higher prevalence of hypertension and cardiovascular disease than other groups. Some have proposed genetics to be the deciding factor; however, this is an unlikely explanation, because American blacks have hypertension at much higher rates than their West African counterparts. Moreover, hypertension pervades other segments of American society in which poverty and social ills are rampant.

  Peter Sterling, the University of Pennsylvania neurobiologist, has written that hypertension in such communities is a normal response to what he calls “chronic arousal,” or stress. In small preindustrial communities, he writes, people tend to know and trust one another. Generosity is rewarded; cheating tends to be punished. When this milieu is disrupted, as in migration or urbanization, there is often an increased need for vigilance. People get estranged from their neighbors. Communities become diverse and more mistrustful. Physical and social isolation often results. Add in poverty, fragmented families, and joblessness, and you get extremely stress-prone populations. The chronic arousal triggers release of hormones, such as adrenaline and cortisol, that tighten blood vessels and cause retention of salt. These in turn lead to long-term changes like arterial wall thickening and stiffening that increase the blood pressure that the body tries to maintain.

  In Sterling’s formulation, nothing is broken (except perhaps “the system”). The body is responding exactly in the way it should to the chronic fight-or-flight circumstances in which it finds itself. If takotsubo cardiomyopathy proves that acute psychological disruption can damage the heart, Sterling’s theories suggest that chronic, low-level stress may be just as harmful. His theories put psychosocial factors front and center in how we think about and approach heart problems. They show that chronic heart disease, unloosed from a Framingham cage, is inextricably linked to the state of our neighborhoods, jobs, and families. Heart disease, in this conception, is no longer strictly biological; it is cultural and political as well. Improving our social structures and relationships becomes not only a quality-of-life issue but also a public health concern.*

  The harmful cardiovascular effects of chronic arousal apply to traditionally white communities, too. One example is the Whitehall study, also conducted by Marmot, of seventeen thousand male workers in the British civil service. In this study, early death and poor health were found to increase stepwise from the highest to the lowest levels of the civil service hierarchy. Messengers and porters had nearly twice the death rate of higher-ranking administrators, even after accounting for differences in smoking, plasma cholesterol, blood pressure, and alcohol consumption. None of these civil servants were poor, in the usual sense. They all enjoyed clean water, plenty of food, and proper toilet facilities. The main ways they differed were in occupational prestige, job control, and other gradients of the social hierarchy. Marmot and his co-workers concluded that emotional disturbance, because of financial instability, time pressures, lack of advancement, and a general dearth of autonomy, drives much of the difference in survival. “Both low-grade civil servant and slum dweller lack control over their lives,” Marmot writes. “They do not have the opportunity to lead lives they have reason to value.”

  Lower socioeconomic classes are not the only ones susceptible to stress-induced heart problems. In the mid-1950s, Meyer Friedman and Ray Rosenman, two American cardiologists working at Mount Zion Hospital in San Francisco, created the idea of a high-achieving personality, which they called type A, that was particularly susceptible to heart disease and was disproportionately found in higher socioeconomic groups. “The type-A person is invariably punctual and greatly annoyed if kept waiting,” they wrote. “He rarely finds time to indulge in hobbies, and when he does, he makes them as competitive as his vocation. He dislikes helping at home in routine jobs because he feels that his time can be spent more profitably. He walks rapidly, eats rapidly, and rarely remains long at the dinner table. He often tries to do several things at once.” They described a characteristic physiognomy of this personality type. “[The type A man] tends to look you straight and quite unflinchingly in the eye. His face looks extraordinarily alert; that is, his eyes are very much alive, quickly seeking to take in the situation at a glance. He may employ a tense teeth-clenching and jaw-grinding posture. His smile has a lateral extension, and his laughter is rarely a ‘belly-laugh.’” In short, they said, the type A person is “aggressively involved in a chronic, incessant struggle to achieve more and more in less and less time.”

  Friedman and Rosenman’s research was girded by the idea “that a person’s feelings and thoughts have an influence on the development of coronary heart disease.” They wrote, “Too many finely executed studies suggested that neither cholesterol nor the fat content of various diets coul
d always explain coronary heart disease. Other factors just had to be playing a part.” In one of their studies, men who fit the type A pattern were seven times more likely to develop arterial disease than was a cohort of (presumably more mellow) municipal union workers and professional embalmers, as well as a group of forty-six unemployed blind men who were assumed to exhibit “little ambition, drive, or desire to compete” because of their lack of sight. The wife of one of the type A subjects told the cardiologists, “If you really want to know what’s giving our husbands heart attacks, I’ll tell you. It’s stress, the stress they receive in their work, that’s what’s doing it.”

  The idea of a stressed but high-achieving subset of American society especially prone to heart disease captured the American imagination. In 1968, the surgeon Donald Effler wrote in Scientific American, “The heart attack is so common among professional people, executives, and men in public office that it has become almost a status symbol. If all the men in these groups who have had coronary attacks were forced to retire … , the shortage of manpower at the top levels of government, industry, and the professions in the U.S. would cripple the nation.”

  The type A link to heart disease has not stood up to modern investigation and is now generally considered an artifact of its time. More recent research has focused on the association of “negative affectivity” traits, such as depression, anxiety, and anger, with heart disease. The strongest evidence has emerged for depression, which seems to be an independent risk factor for coronary artery disease and increases the risk of poor outcomes, including death, after a heart attack. How does depression affect heart health? Possible mechanisms include elevating blood pressure, causing vascular inflammation, disturbing autonomic nervous system function, and increasing blood clotting. Also probably playing a role are unhealthy behaviors associated with depression, such as physical inactivity, smoking, and failure to take medications or adhere to medical advice.

  Today a massive amount of epidemiological data associates heart disease with chronic emotional disorder—or disruption of the metaphorical heart. For example, individuals in unhappy marriages are at a much higher risk for heart disease than those in more joyous unions. The risk of myocardial infarction and death increases dramatically in the year following a broken romance.

  These associations hold true even for animals we would not consider needing social connection. For example, in a study in the journal Science, researchers fed caged rabbits a highcholesterol diet to study its effect on heart disease. Surprisingly, they found that animals in high cages got much more cardiovascular disease than ones in cages near the floor. The scientists investigated air circulation and other possible factors, without success. Then they discovered that the technician who delivered food played more often with the animals in the lower cages than with the ones near the ceiling. So they repeated the study, randomly dividing the rabbits into two groups: one group that was removed from their cages and petted, held, talked to, and played with, and another that remained in their cages and was ignored. The first group had 60 percent less aortic atherosclerotic surface area on autopsy than the second, despite having comparable cholesterol levels, heart rate, and blood pressure.

  Socially stressed laboratory monkeys also develop more heart disease than matched controls. In another study in Science, male monkeys that had stranger monkeys introduced into their cages, often in the presence of an estrogen-laden female monkey, resulting in fights for dominance and less social huddling, developed more coronary artery disease than a control group of monkeys that was not stressed, even though cholesterol levels, blood pressure, blood sugar, and body weight were similar between the two groups. “Psychosocial factors,” the authors concluded, “thus may help explain the presence of coronary artery disease (occasionally severe) in people with low or normal serum [cholesterol] and normal values for the other ‘traditional’ risk factors.”

  We paid little attention to “psychosocial” factors during fellowship. The focus of our seminars was on pressure-volume loops, cardiac work cycles, resistance of fluid-filled pipes, and capacitance of fluid-filled chambers. We concentrated on clinical trial design, biological mechanisms, and understanding the heart as a machine. As with most academic training programs, the fact that there was an emotional world that could damage (or heal) this pump was largely ignored.

  Ironically, the view that heart disease results from unfulfilled social or psychological needs was widely accepted in primitive societies. That is almost certainly how people thought about heart disease in rural Punjab in the 1950s. Doctors at the hospital where my grandfather was pronounced dead did not know about the damaging effects of cholesterol and hypertension (Framingham results had not yet been broadly disseminated). They would have explained my grandfather’s heart attack as the result of a sudden emotional shock (as when your neighbors bring a dead cobra into your home while you are having lunch with your family), or the years of social and financial struggle he endured after the Partition of India, or the loss of social connectivity that resulted from the fracturing and large-scale displacement of communities that had lived together for centuries, and in a sense they would have been right. Stress-induced surges of adrenaline can cause a stable atherosclerotic plaque to fissure and rupture, forming a thrombosis that can acutely block the artery and stop blood flow, thus causing a heart attack. Starved for oxygen, tissue begins to die. Irreversible cellular injury occurs within twenty minutes. And then, frequently, death.

  Medicine today conceptualizes the heart as a machine. With advances in technology, perhaps this was inevitable. Drugs and devices have been responsible for much of the improvement in cardiovascular mortality over the past fifty years.

  However, this narrow focus on biological mechanisms has hurt patients. We have overused stents and pacemakers. We have moved away from the emotional heart to a narrow focus on the biomechanical pump. The American Heart Association still does not list emotional stress among the key modifiable risk factors for heart disease—perhaps in part because serum cholesterol is so much easier to reduce than emotional and social disruption. We need a better way, one that recognizes the power and importance of emotions that the heart—the metaphorical heart—was believed to house for millennia. Though we know today that the heart is not the repository of the affections, it nevertheless remains the physiological canvas upon which our emotions are most easily written.

  *The British were under no such delusions. When Churchill visited the White House in May 1943, he asked his own physician whether he had noticed that Roosevelt was “a very tired man.” He added, ominously, “The Americans here cannot bring themselves to believe that he is finished.”

  *Thirty years later, in 1884, Robert Koch, a German physician, isolated the pathogen Vibrio cholerae, which causes cholera.

  *In later years, Framingham investigators added about a thousand ethnic minority patients to their study to try to understand why heart disease occurs disproportionately in certain groups and to identify novel risk factors.

  *The National Institutes of Health has started such a study. Named Mediators of Atherosclerosis in South Asians Living in America, or MASALA, it has enrolled about nine hundred South Asian men and women in two large metropolitan areas, the San Francisco Bay Area and Chicago. Researchers are focusing on novel risk factors, including malignant forms of cholesterol (previous research has suggested that South Asians may have smaller and denser cholesterol particles that are more prone to causing hardening of the arteries), as well as other social, cultural, and genetic determinants.

  *Sterling’s theory, allostasis, is a new way to think about human physiology. The traditional theory taught in medical school, homeostasis, holds that organ systems work together to maintain physiological balance. For example, when blood pressure drops acutely, the heart speeds up and the kidneys retain sodium and water, propelling blood pressure back to normal. If body temperature falls, we shiver to generate heat, blood vessels constrict to conserve heat, and we warm up. Homeostasis is about
preserving constancy in the face of changing conditions. As a model for explaining human physiology, it does pretty well.

  However, there are aspects of the human condition that homeostasis cannot explain. For instance, blood pressure often fluctuates minute to minute. If the body is supposed to be maintaining an optimal set point, it doesn’t seem to be doing a very good job. Blood pressure also increases steadily throughout childhood and adulthood. It is often constant until about age six, when children enter school, but then it rises quickly as kids detach from their parents and must become vigilant at defending against real or perceived threats. By age seventeen, almost half of all boys have blood pressures in the pre-hypertensive range, and about 20 percent have full-blown hypertension. Why does the blood pressure set point drift upward? To explain these things, experts like Sterling have proposed an alternative theory to homeostasis: allostasis.

  Allostasis is not about preserving constancy; it is about calibrating the body’s functions in response to external as well as internal conditions. The body doesn’t so much defend a particular set point as allow it to fluctuate in response to changing demands, including those of one’s social circumstances. Allostasis is, in that sense, a politically sophisticated theory of human physiology. Indeed, because of its sensitivity to social circumstances, allostasis is in many ways better than homeostasis for explaining modern chronic diseases.