Psychological conditioning of angina pectoris
It is a widely held view that angina pectoris results from a mismatch between restricted coronary artery blood flow and an increased myocardial workload. The hypothesis was first proposed by Keefer and Resnick more than 70 years ago (1), yet many clinical observations do not accord with this view (2). Advanced multi-vessel coronary artery disease may cause congestive heart failure in patients who had never suffered from angina. The very converse is also true, namely, typical angina may be experienced by patients with angiographically intact coronary arteries.
If the provocative factor is due to inadequate oxygen delivery in relation to the cardiac workload, it is difficult to reconcile the striking divergence between the efforts required to induce pain on different occasions. I cite but a few of the numerous clinical observations: the truck driver who carts heavy furniture without experiencing chest discomfort, but can not walk a block with his wife without resorting to nitroglycerin; the man who has consistent angina walking from car to office though it is downhill, and is free of angina when climbing up the steep incline to the car park after work; or the meat packer who never experienced angina when carrying on his shoulder a 20 kg slab of beef into a freezer room, but is often halted by severe retrosternal squeezing when merely hiking.
Clinicians recognize the stereotypic pattern in the occurrence of angina. A patient may be able to exert strenuously indoors without any discomfort, but be limited while walking outdoors with ambient temperatures similar in both settings. Modest activity on first arising in the morning is more likely to precipitate angina than greater exertion later in the day.
The threshold for pain is lower with the onset of activity than during its continuance. For example, the golfer afflicted with angina is frequently aware of chest pressure which occurs at the initial tee-off, yet is rare thereafter while traversing a far more taxing terrain. Customary work, although arduous, usually does not induce angina. At times, seemingly innocuous stimuli, minor psychological stresses, or miniscule efforts can set off anginal episodes. While the rate-pressure product is a fair index of myocardial oxygen consumption, it bears little concordance with the onset of angina (3).
Many such clinical observations suggest the operation of other pathophysiological mechanisms in the genesis of angina. That psychological stress is implicated is a clinical truism. A number of times while witnessing provocation of angina by intense emotion, I did not detect a change in heart rate or blood pressure. I recall a patient who developed angina only upon receiving a telephone call in the early afternoon. His heart rate at the time remained at 65 bpm and blood pressure continued at 132/76 mmHg. A careful history revealed that one afternoon five years earlier, he learned by telephone that a truck had killed his young daughter on her way home from grammar school. I also recall a patient who consistently developed angina when he walked down to the cellar of his home where, a few years earlier, he found his teenage son hanging. An exercise stress test that accelerated his heart rate to 144 bpm and raised his blood pressure to 180/70 mmHg did not provoke angina.
These experiences are reminiscent of a Pavlovian conditioned reflex. In the two patients described, the stimulus was a shocking memory. Psychologists have designated these phenomena as nocebo responses, or negative placebo effects.
The following study illustrates the reality of the nocebo response. Psychology students, participating in an experiment at the University of California, were warned that they might get a headache from a mild electric current being passed through their heads. Two-thirds of the students reported experiencing pain. The pain persisted even after they were informed that there had been no electric current. In fact, the pretended electric current resulted in a real headache (4). In another study, when hospitalized patients were given sugar water and told it was an emetic, 80% vomited shortly thereafter.
These observations suggest the possibility that a similar type of nocebo-like conditioning plays a role in angina pectoris. I am convinced of this, having once succeeded in deliberately conditioning the provocation of angina pectoris. The patient was a 40-year-old truck driver with severe multi-vessel coronary artery disease. At the time, there were no effective anti-anginal drugs. It was long before revascularizing cardiac surgery or angioplasty.
The patient consistently experienced retrosternal pressure and exhibited 3-4 mm of planar ST segment depression after 44 crossings of a small staircase. This was the so-called Master's Two-step Test. I found no ready explanation for the curious fact that in each of the five tests he was compelled to stop at precisely 44 crossings of the two-step. This study had taken place over several months and at various times of the day.
Thereupon I initiated the following study: The exercise testing was conducted in exactly the same manner except the count of each crossing, which hitherto had been called out, was now silent. As he reached 28 crossings, I called out 40 then 41, and so forth. He seemed startled at the more rapid approach of the end of exercise, but after the 29th crossing (at the count of 41) he complained of angina and by the 32nd crossing miscounted as 44, he was compelled to stop. The electrocardiographic pattern was nearly identical to that noted on prior occasions when he traversed the two-step 44 times (the electrocardiographic tracings are available in reference 5).
Exercise tests with such miscountings were repeated several times with an identical result. However, when there was a loud count and he was stopped after 32 crossings, there was neither pain nor any ST segment deviations. There was little concordance between the degree of tachycardia and the occurrence of angina.
This experience demonstrated that angina could be induced by verbal conditioning. In fact, specific numbers had come to communicate a level of intolerable stress with profound biological consequences. The observation has substantial implications for understanding the pathogenesis of angina. Suggested is the operation of higher nervous mechanisms, and that neural inputs from brain to heart may determine the occurrence of the classical ischemic pain. Whether the mechanism is ultimately through vasospasm as encountered in Prinzmetal's angina, through effects on endothelium, or by the release of nociceptive cytokines remains to be established.
Irrespective of the underlying mechanism, there are important clinical implications. The physician needs to search for a conditioning paradigm in the patient presenting with angina. There are rewards for such painstaking history taking. For example, in the two cases reported wherein the death of a child was responsible, psycho-therapy resolved the angina.
-Originally published on 29 February 2000
The patient G.A., here described, first presented in March 1956 and died suddenly one year later, barely having reached his 41st birthday. Nearly every member of his family had precocious coronary artery disease.
No patient ever affected me as much, no patient ever taught me as much, no patient ever changed my style of practice as much as this truck driver. Though unschooled, he was self-educated and prodigiously well-read, including the works of Pavlov, who first described the conditioned reflex.5
A relatively innocuous count-down provoked angina and profound ST segment changes. That psychological factors can predispose to episodes of anginal discomfort was already appreciated by Heberden, who first described the syndrome. The experience of triggering angina by a verbal cue, though singular, nevertheless cast a powerful light on the pathogenesis of this common syndrome.
- 13 September 2008
1. Keefer CS, Resnik WH. Angina pectoris: a syndrome caused by anoxemia of the myocardium. Arch Intern Med. 1928;41:769.
2. Levine SA. Some puzzling points concerning angina pectoris. Am J Cardiol. 1959;1:19.
3. Wayne EJ, Laplace LB. Observation of angina of effort. Clin Sci. 1933;1:103.
4. Hahn RA. The Nocebo phenomenon scope and foundations. In The Placebo Effect, Harrington, A, ed. Cambridge, MA: Harvard University Press; 1997.
5. Lown B. Verbal conditioning of angina pectoris exercise testing. Am J Cardiol. 1977;40:630-634.
Date Posted: 13 September 2008