Heart Mind

: 2021  |  Volume : 5  |  Issue : 1  |  Page : 1--3

Spotlight on the relationship between heart disease and mental stress

Meiyan Liu 
 Department of Cardiology, Beijing Anzhen Hospital Affiliated to Capital Medical University, Beijing, China

Correspondence Address:
Prof. Meiyan Liu
Department of Cardiology, Beijing Anzhen Hospital Affiliated to Capital Medical University, No. 2 Anzhen Road, Chaoyang District, Beijing 100029

How to cite this article:
Liu M. Spotlight on the relationship between heart disease and mental stress.Heart Mind 2021;5:1-3

How to cite this URL:
Liu M. Spotlight on the relationship between heart disease and mental stress. Heart Mind [serial online] 2021 [cited 2023 Feb 8 ];5:1-3
Available from: http://www.heartmindjournal.org/text.asp?2021/5/1/1/312307

Full Text

Research on the correlation between mental stress and heart disease has been ongoing for many years, and the association between the two has mainly focused on autonomic function.[1] More than 20 years ago, I worked in the coronary care unit of the People's Hospital of Peking University, and as a critical care physician I observed many interesting phenomena in this field, and started a series of studies on psychological heart disease and neuroendocrine-related mechanisms.

In my early clinical work, with many patients who suffered from myocardial infarction or arrhythmia, I found when I pursued their medical history that a considerable number of them had emotional triggers such as high mental stress, tension, anxiety, anger and so on. What is striking is that after a myocardial infarction induced by mental stress, the patient has to suffer again in the coronary intensive care unit, the pain of not having a loved one with them and the fear of death, which often further worsens the disease, and this mental stress further drives the development of the disease. Early help offered to patients to control their emotions to cope with stress rationally will significantly improve cardiovascular outcomes.[2] Of course, one would also face skepticism from peers who tended to believe that the therapeutic value of emotional psychological factors was not great and that focusing on the patient's psychology would undermine the professional image of the cardiovascular physician. At that point in time, we were far from recognizing that a range of emotional factors, including depression and anxiety, could dramatically alter the progression of cardiovascular disease and the series of mechanisms behind it.

As research continued, it was gradually found that the key to the development of psychological heart disease is that emotion-related mental stress brings about sympathetic hyperexcitability, which in turn triggers cardiac and vascular injury.[3] The mechanism of injury underlying the stress response can be further investigated by comparing the changes in adrenaline levels in the coronary sinus and peripheral blood before and after mental stress.[4] Previous studies have suggested that the mental stress response relies on adrenaline rather than noradrenaline, because the changes in adrenaline in peripheral blood measured by standard methods are significant, while noradrenaline does not change much.[5] This view now seems to be incorrect, as sympathetic excitation triggers an increase in adrenaline secretion, but this response is sub-regional and varies individually, for example, stress triggers an increased cardiac response and a weaker or even undetectable response in the skeletal muscle.[6] This indicates that adrenaline levels in the heart increase under stress, while adrenaline in the skeletal muscle does not increase significantly. Increased adrenaline in the heart can lead to excessive cardiac sympathetic activation, which in turn can lead to serious cardiovascular adverse events.[7]

Numerous studies have shown cardiac reactions happen in populations when large disasters such as earthquakes and incidents of war occur, suggesting a clear association between stress and cardiac injury,[8] as in the case of 9/11 when American doctors found frequent discharges of pacemakers in patients with these implants. This is also the case with the occurrence of stress cardiomyopathy, where both positive and negative emotions can trigger myocardial damage, which is very evident in stockholders in the face of sudden changes in the stock market.[9] It is worth considering whether such occurrence of heart disease during disasters is specific or universal. “Emotional earthquakes” can induce heart disease, as sympathetic nerves are activated under stress, which leads to platelet activation and thrombosis;[10] they can also lead to blood pressure fluctuations, causing plaque rupture and myocardial infarction;[11] at the same time, high-frequency electrical activity in sympathetic nerves can cause massive release of neuropeptide Y, leading to coronary artery spasm, triggering ischemic heart disease.[12]

This is also the case with panic attacks, where patients often have extremely strong cardiac symptoms and near-death experiences, which we used to say were not cardiac disease, but then patients are usually found clinically to develop various cardiac complications, including atrial fibrillation, ventricular arrhythmias, myocardial ischemia, coronary spasm, and even myocardial infarction.[13] It is currently believed that acute myocardial infarction and the increased risk of sudden death triggered by panic attacks arises mainly from sympathetic excitation, but skeletal muscle excitation is not evident during the stress period, which some scholars consider difficult to explain.[14] The occurrence of panic attacks is associated with neurotransmitter dysfunction in the brain, and effective treatment with selective serotonin reuptake inhibitors (SSRIs) suggests that the transport of 5-hydroxytryptamine (Serotonin, 5-HT) in the central nervous system may be defective in this group of patients.[15] During panic attacks, blood sampling from the jugular vein of patients revealed enhanced 5-HT transport in the central nervous system (CNS).[16] However, some animal experiments have shown anxiolytic effects of 5-HT neurons in the raphe nucleus of the brain, and the enhanced transport has no effect on the central pathogenesis of panic attacks.[17]

Mental stress is very important in the development of hypertension, and there are many biological markers associated with mental stress, such as increased release of adrenaline from sympathetic nerves and increased in situ synthesis when the body is subjected to chronic stress.[18] Biopsy of sympathetic nerves above forearm veins in hypertensive patients revealed an increase in phenylethanolamine N-methyl transferase, a marker of mental stress exposure, while this indicator was lacking in patients without hypertension.[19] Monitoring of microneural currents in hypertensive patients revealed that they experienced repeated firing of sympathetic nerve fibers during each cardiac cycle, while healthy individuals did not, which is more like the effect of mental stress.[20]

In summary, the heart is not only the physical pump of the organism but also senses changes in the needs and emotions of the organism. External changes, by modulating vagal and sympathetic functions, can lead to a series of changes in the organism such as inflammatory responses and altered hormone levels.[21]

The autonomic function of the body is altered in stressful conditions, showing increased cardiac output and faster heart rate. Prolonged standing and anxiety can induce vagal activation, which in turn leads to vasodilation, reduced heart rate, and even hypotensive syncope.[22] Autonomic control of the heart can be studied by affecting the vagal or sympathetic activation state with atropine or β-blockers.[23] By measuring the amount of noradrenaline released by the cardiac sympathetic nerve in different states, it is possible to study the cardiac sympathetic response in anxious and depressed patients, which helps us to better understand stress coping and potential mobilization during daily work and how to avoid unnecessary damage to the heart.[24]

Prevention and control of sudden death is very challenging for physicians, and a large proportion of patients suffering sudden death have a disease base of coronary atherosclerosis, usually asymptomatic and unappreciated, mostly induced by acute mental stress.[25] Therefore, the exploration of cardiac markers with predictive value and the detection of asymptomatic stenosis and unstable plaques in coronary arteries are of great importance for the prevention of sudden death. However, the greatest difficulty currently lies in the prevention of cardiac stimulation from altered autonomic function under acute stress, which requires what we term dual psychological and cardiac protection.


In the last decades, a large number of studies have confirmed the inextricable relationship between mental stress and heart disease. This article describes the mechanism of stress-induced neuroendocrine alterations in the body that cause cardiac damage and related treatment strategies. Importantly, it addresses current concerns over stress-induced sudden death and the preventative role of dual psychological and cardiac protection. The aim is to enhance the clinical workers' understanding of the duality of physical and emotional cardiac functions in disease and strengthen provision of dual psychological and cardiac protection.

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Conflicts of interest

Prof. Meiyan Liu is the Executive Editor-in-Chief of the Heart and Mind journal.


1Hildreth V, Anderson RH, Henderson DJ. Autonomic innervation of the developing heart: Origins and function. Clin Anat 2009;22:36-46.
2Cohen BE, Edmondson D, Kronish IM. State of the art review: Depression, stress, anxiety, and cardiovascular disease. Am J Hypertens 2015;28:1295-302.
3Toukhsati SR, Hare DL. Towards optimal heart failure care: Couples-oriented strategies to improve patient adherence and health outcomes. Curr Cardiol Rev 2016;12:243-8.
4Wortsman J. Role of epinephrine in acute stress. Endocrinol Metab Clin North Am 2002;31:79-106.
5Wong DL. Epinephrine biosynthesis: Hormonal and neural control during stress. Cell Mol Neurobiol 2006;26:891-900.
6den Hartog CR, Blandino KL, Nash ML, Sjogren ER, Grampetro MA, Moorman DE, et al. Noradrenergic tone mediates marble burying behavior after chronic stress and ethanol. Psychopharmacology (Berl) 2020;237:3021-31.
7Barman SM. 2019 Ludwig Lecture: Rhythms in sympathetic nerve activity are a key to understanding neural control of the cardiovascular system. Am J Physiol Regul Integr Comp Physiol 2020;318:R191-205.
8Burg MM, Soufer R. Post-traumatic stress disorder and cardiovascular disease. Curr Cardiol Rep 2016;18:94.
9Schwartz BG, Pezzullo JC, McDonald SA, Poole WK, Kloner RA. How the 2008 stock market crash and seasons affect total and cardiac deaths in Los Angeles County. Am J Cardiol 2012;109:1445-8.
10Hjemdahl P, Wallén NH. Calcium antagonist treatment, sympathetic activity and platelet function. Eur Heart J 1997;18 Suppl A: A36-50.
11Steptoe A, Kivimäki M. Stress and cardiovascular disease. Nat Rev Cardiol 2012;9:360-70.
12Lundberg JM, Franco-Cereceda A, Lacroix JS, Pernow J. Neuropeptide Y and sympathetic neurotransmission. Ann N Y Acad Sci 1990;611:166-74.
13Machado S, Sancassiani F, Paes F, Rocha N, Murillo-Rodriguez E, Nardi AE. Panic disorder and cardiovascular diseases: An overview. Int Rev Psychiatry 2017;29:436-44.
14Caldirola D, Schruers KR, Nardi AE, De Berardis D, Fornaro M, Perna G. Is there cardiac risk in panic disorder? An updated systematic review. J Affect Disord 2016;194:38-49.
15Bandelow B, Michaelis S, Wedekind D. Treatment of anxiety disorders. Dialogues Clin Neurosci 2017;19:93-107.
16Tanahashi S, Tanii H, Konishi Y, Otowa T, Sasaki T, Tochigi M, et al. Association of serotonin transporter gene (5-HTTLPR/rs25531) polymorphism with comorbidities of panic disorder. Neuropsychobiology 2020;1-9. Available from: https://www.karger.com/Journal/OnlineFirst/224082.
17Liu M, Wei W, Stone CR, Zhang L, Tian G, Ding JN. Beneficial effects of trimetazidine on expression of serotonin and serotonin transporter in rats with myocardial infarction and depression. Neuropsychiatr Dis Treat 2018;14:787-97.
18Peng XY, Huang Y, Wang XL, Cao LF, Chen LH, Luo WF, et al. Adrenergic β2-receptor mediates itch hypersensitivity following heterotypic chronic stress in rats. Neuroreport 2015;26:1003-10.
19Huang C, Zhang S, Hu K, Ma Q, Yang T. Phenylethanolamine N-methyltransferase gene promoter haplotypes and risk of essential hypertension. Am J Hypertens 2011;24:1222-6.
20Grassi G, Cattaneo BM, Seravalle G, Lanfranchi A, Mancia G. Baroreflex control of sympathetic nerve activity in essential and secondary hypertension. Hypertension 1998;31:68-72.
21Coote JH, Chauhan RA. The sympathetic innervation of the heart: Important new insights. Auton Neurosci 2016;199:17-23.
22Ginty AT, Kraynak TE, Fisher JP, Gianaros PJ. Cardiovascular and autonomic reactivity to psychological stress: Neurophysiological substrates and links to cardiovascular disease. Auton Neurosci 2017;207:2-9.
23Grandi E, Ripplinger CM. Antiarrhythmic mechanisms of beta blocker therapy. Pharmacol Res 2019;146:104274.
24Tank AW, Lee Wong D. Peripheral and central effects of circulating catecholamines. Compr Physiol 2015;5:1-5.
25d'Amati G, Cerbelli B, Giordano C. Coronary atherosclerosis and sudden cardiac death in the young: Another face of the culprit, another way of striking? Int J Cardiol 2018;264:28-9.