Evaluating the Role of Stress in the Incidence of Cardiovascular Disease

IntroductionLazarus and Folkman (1984) define stress as a relationship between an individual and their environment that is appraised by the individual as taxing or exceeding their resources, thus endangering their physical well-being. Similarly, biological stress is a process of stimulus and response a homeostatically altered state following perceived endangerment or emotional stimuli that evokes a myriad of adaptive reactions (Holsboer Ising, 2010). These adaptive responses are part of an evolutionary mechanism designed to react to danger. However, this mechanism is ill-suited to prolonged use, causing manifold physiological detriments (Milosevic McCabe, 2015).

Cardiovascular diseases (hereafter referred to as CVDs) are ailments affecting the heart and vascular systems of the body (WHO, 2017). Connections between stress and CVD have been observed for decades, with considerable research devoted to establishing the causal impacts of psychological and environmental factors on both biological processes (Steptoe Kivim ki, 2013). As such, in this essay I will examine these connections, and evaluate the role of stress in the establishment of CVD with particular focus given to their biological processes, and how psychological and environmental factors exacerbate these issues.

Cortisol the HPA AxisThe HPA Axis, put simply, is a sequential mechanism. A perceived threat causes a release of Corticotropic Releasing Hormone from the Hypothalamus (H), which in turn causes a release of Adrenocorticotropic Hormones from the anterior Pituitary (P), which travel to Adrenal Glands (A) above the kidneys. These glands are made up of the Adrenal Medulla and the Adrenal Cortex, releasing Adrenaline and Cortisol respectively (Dedovic et-al, 2009) the latter incurring harm when overused. Cortisol itself is a Glucocorticoid produced by the zona fasciculata, the adrenal cortex s midsection, and is the inhibitory hormone of the parasympathetic nervous system (Herman et-al, 2005).

High cortisol levels are associated with risk of CVD, a finding replicated across many studies. Namely, Manenschijn et-al (2013) using hair analysis Vogelzangs et-al (2010) using urinary analysis Kumari et-al (2011) using saliva analysis and Whitworth et-al (2005) using blood analysis. The modalities used to collect data twinned with its longstanding replicability bring increased validity to these findings. The lattermost study examined incidence of CVD in the clinical population of Cushing s Disease, a state of glucocorticoid overexposure. It was found that Cushing s sufferers were at higher risk of hypertension, heart failure, and arrythmia. This falls in line with other research such as Wei et-al (2004) who found glucocorticoid prescri ption can cause similar CVD incidence. Additionally, Cortisol s vasoconstrictive properties (Walker et-al, 1996) and detrimental effect on fat metabolism (Ceccato et-al, 2020 Vehmeijer et-al, 2021), increase atherosclerosis incidence (Dekker et-al, 2008). Atherosclerosis refers to fatty deposits within blood vessels, causing narrowing and blockage therein. This in turn can cause cardiomyopathies and ischemic heart disease (Marzilli et-al, 2012). When fat deposits dislodge, they can cause pulmonary embolism, myocardial infarction, and stroke (Katakami, 2017). In some clinically overstressed populations, the overproduction of cortisol can be an issue in need of medical management. These treatments include anxiolytics to reduce to impact of stress in the brain, and beta-blockers to reduce the effect of noradrenaline on the cardio-vascular system (American Addiction Centre, 2015).

Personality subtypes can exacerbate the effects of stress. Friedman Rosenman s (1959) study of personality subtypes and their incidence of CVD found that those with Type A personalities show a higher incidence of CVD, supposedly because of their highly-strung nature. However, attempts to replicate these findings found mostly inconsistencies and negative results, concluding that a two-factor personality matrix for explaining CVD was reductive (Espnes, 2016). This poor replicability led to the evolution of the theory beyond the purview of Friedman Rossman. Thus, Type D Personality was theorised (Sahoo et-al, 2018). This subtype has shown a greater predisposition towards CVD (Denollet et-al, 2000), due to its tendency toward negative affectivity and social inhibition, both of which are linked to CVD (Denollet, 2005). This subtype benefits from modern methods of cortisol analysis which support this assertion (Schiffer et al, 2006). Additionally, Type D personality has shown to increase incidence of stress-induced immune dysregulation in a similar fashion to depression (Masafi et-al, 2018). In regard to treatment, mindfulness meditation has been shown to reduce incidence of CVD in Type D personalities (Nykl c ek, 2012).

Trauma plays a large role in the levels of cortisol in the body. Hopf et-al (2020) found that recently bereaved individuals will have higher levels of cortisol than the general population, with severity of bereavement being an exacerbating factor. This denotes that bereaved individuals would have a higher incidence of CVD, which is supported by research into Takotsubo Cardiomyopathy (TCM), a weakening of the heart s musculature following trauma (Schwartz et-al, 2012 Komamura et-al, 2014). However, this disease is not limited to the bereaved. Thurston et-al (2017) and Boss et-al (2018) both observed similar incidence of TCM in abuse survivor populations, in addition to increased levels of cortisol. Aspirin has been shown to reduce incidence of infarction, and a combination therapy of ACE inhibitors and beta blockers has been shown to delay heart failure though it should be noted that there are no internationally recognised treatments of TCM, and greater success has been found in treating the underlying trauma (Ahmad et-al, 2021). Such treatments include immediate propranolol to reduce long-term PTSD-related cortisol heightening (Viava, 2003), and trauma therapies for underlying issues (Shannon et-al, 2012).

Telomere ErosionThe biological process of telomere erosion can also lead to CVD when impacted by stress. Telomeres act as protective buffers at the end of chromosomes, preventing DNA from damage during cellular reproduction (Aubert Lansdorp, 2008). Over time telomeres shorten, causing cells to reproduce abnormally and pro-inflammatorily. Haycock et-al s (2014) meta-analysis found shorter telomeres associated with increased incidence of CVDs such as myocardial infarction (Brouilette et-al, 2003), stroke (Ding et-al, 2012), ischemic heart disease (Weischer et-al, 2012), and atherosclerosis (Willeit et-al, 2010 Yegorov et al, 2021). This process can be accelerated by stress, likely due to cortisol decreasing supplies of telomerase, a telomere replenishing enzyme (Choi et-al, 2008 Epel et-al, 2010). Supporting this assertion, a recent meta-analysis found that high salivary cortisol levels were correlated with reduced telomere length and repairability (Jiang et-al, 2019). However, many studies examining this link use blood-leukocyte telomere analysis, an un-invasive but nonetheless removed alternative to analysing telomeres in cardiac tissue reducing the validity of findings (Haycock et-al, 2014). Some treatments have had minor success, such as telomerase-targeting gene therapies (Mart nez Blasco, 2017). However, current capacity to directly negate telomere erosion is limited. Methods of reducing telomere erosion focus on lifestyle changes, such as exercise (Puterman et-al, 2010) and specifically yoga (Kumar et-al, 2014), that impact telomeres indirectly.

Psychological thinking styles can also impact telomere length. Depressive-rumination is a thinking style of pathological overanalyses incurring sadness, and is associated with several mood disorders (Hoeksema, 2000). Rumination, and its associated disorders, have shown links to increased stress hormone levels (McEwen, 2003 Morrison O`Connor, 2005). As such, independent of telomeres, depressive-rumination has been linked to increased CVD incidence (Busch et-al, 2017) and recovery-time (Radstaak, 2011). However, it has also been linked to hastened telomere erosion, as have the mood disorders with which it is associated (Simon et-al, 2006), cementing its CVD risk. This assertion is further supported Hartmann et-al s (2010) finding that major depressive patients possess shorter telomeres than controls, however severity of condition and undertaking of therapy showed no significant impact upon telomere length the latter finding again necessitating lifestyle changes over therapeutics as treatment. A follow-up study to Puterman et-al (2010) found that exercise moderates not only telomere erosion, but reactivity to rumination also (Puterman et-al, 2011) furthering its viability as a treatment for telomere-related CVD. Additionally, Hoge et-al (2018) found that mindfulness meditation, a suggested treatment for rumination-predisposed mood disorders (Moral, 2017), also slows telomere erosion. However, this finding is disputed by Dasanayaka et-al s (2020) systematic literature review, concluding that results require further investigation. Moreover, similar types of mental training have shown little to no effect on telomeres (Puhlmann et-al, 2019).

Environmentally, trauma too impacts telomere erosion. Salivary DNA testing of 3707 children found evidence of paternal bereavement impacting telomere length (Mitchell et-al, 2017). This finding is supported in wider literature, with PTSD sufferers possessing shorter telomeres than controls (Aas et-al, 2019). However, as these studies again use leukocyte telomeres rather than cardiac tissue, it remains unclear how well they relate to CVD. A more firmly founded link with CVD can be observed in the environmental factor of Oxidative Stress Triggers. Oxidative stress is the process by which oxidation damages cells, caused by overproduction of oxidising species or underuse of antioxidant defences (Sies, 2000). Due to oxidative damage being harder to repair in telomeric DNA, oxidative stress can reduce telomere length and increase incidence of aforementioned CVDs (Boonekamp et-al, 2017) as well as having its own inflammatory links to atherosclerosis and myocardial infarction independent of its effect upon telomeres (Steven et-al, 2019). Such oxidative stress can be caused by obesity, smoking, alcoholism, or drug abuse (Cunha-Oliveira et-al, 2013), all of which have shown increased frequency in stressed individuals (Duffing et-al, 2014) making this an environmental factor. Additionally, these oxidative stress triggers are more prevalent amongst low socioeconomic status individuals (McLaren, 2007 Glei Weinstein, 2019 ), which may explain why low SES is associated with increased rates of telomere erosion (Mitchell et al, 2018) and increased incidence of CVD (Zhang et-al, 2021). Antioxidant vitamins have shown little success in reversing the effects of oxidative stress upon telomeres and cardiovascular tissue (Heistad et-al, 2009). However, beta-blockers (Nakamura et al, 2011), anti-inflammatory immunomodulation (Steven et-al, 2019), and molecular hydrogen (Lebaron et-al, 2019) have shown success in reducing oxidative stress effects.

Immune DysfunctionAs another biological point, stress can also cause CVD through its impact upon the immune system. Stress hormones have been linked to targeted local expression of pro-inflammatory cytokines (Elenkov Chrousos, 2007), which aid in swelling vascular endothelium and transforming local healthy monocytes into lipid-laden foam cells, increasing incidence of atherosclerosis (Gu et-al, 2012). Supporting this, it has also been found that salivary cortisol levels correlate to degrees of atherosclerosis in carotid arteries (Dekker et-al, 2008). However, glucocorticoids have been shown to reduce overall production of pro-inflammatory cytokines and detrimentally impact lymphocyte proliferation (Elenkov Chrousos, 2007) thus leaving the system vulnerable to disease and less capable of healing (Marketon Glaser, 2008). Accordingly, harmful external pathogens can more easily take root in the body, increasing atherosclerosis incidence and reducing the body s ability to heal itself from CVDs (Rosenfeld Campbell, 2011 Horckmans et-al, 2017). However, it should be noted that the link between infection and atherosclerosis is unclear. Some studies support a direct causal link between certain pathogens and atherosclerosis (Streblow et-al, 2001), whereas others support a more indirect proxy-link between immune response and atherosclerosis (Rosenfeld Campbell, 2011).

Stress hormones released by psychological disorders can cause similar effects upon the immune system. Depressive and anxious disorders have been shown to increase basal cortisol levels, and decrease the rate at which cortisol subsides after stress (Burke et-al, 2005). This in turn has been linked to the local proliferation of pro-inflammatory cytokines in sufferers (Glaser, 2002), increasing atherosclerosis incidence and severity (Kop Gottdiener, 2005). Additionally, this inflammation can be exacerbated by reduced levels of serotonin. This reduction is prevalent amongst many psychological disorders (Lin et-al, 2014), and leads to an inhibition of lymphocyte production (Robson et-al, 2017) in turn detrimentally impacting the immune system and allowing external pathogens to, as aforementioned, increase atherosclerosis incidence. Moreover, the symptoms of mental disorders, such as negative affect, social isolation, pessimism, etc, have been shown individually to exacerbate immune dysregulation and CVD incidence (Reed Raison, 2016) further cementing the assertion that mental disorders can increase immune-related CVD risk. Increased exercise has been shown to modulate basal cortisol levels in mentally unwell individuals, thus mediating its immune-deregulatory effects (Beserra et-al, 2018). Due to the positive effect exercise has upon cardiovascular tissues (Fiuza-Luces et-al, 2018), this treatment option represents a holistic and non-medical solution. However, pharmaceutical strategies have shown equal success, with anti-depressants shown to reduce the detrimental effect mental disorders can have upon lymphocyte proliferation (Leonard et-al, 2001).

As aforementioned, socioeconomic status effects CVD incidence, and has shown particular links to financial stressors and poor nutritional intake (Lazzarino et-al, 2013 Psaltopoulou et-al, 2017). This effect may be further exacerbated by immune dysregulation. Low SES adolescents have shown greater activation of C-reactive proteins, a marker of immune-related inflammation (Brummett et-al, 2013). These inflammatory markers have been shown to be associated with atherosclerosis in later life (Pollitt et-al, 2007). Supporting this, low SES individuals have shown greater levels of basal cortisol, which as stated prior causes immune dysregulation through the irregular release of pro-inflammatory cytokines (Cohen et-al, 2006). However, the longevity of this impact is debated. A recent meta-analysis has suggested that exposure to early-life SES stressors can cause an uptick in inflammatory markers, which subside over time as a person ages (Milaniak Jaffee, 2019). This however runs contrary to a majority of Sensitive Period models, many of which agree that SES stressors during critical periods of development cause lifelong health consequences (Morey et-al, 2015 Jones et-al, 2019), particularly in regards to immune-inflammatory atherosclerosis (Needham et-al, 2015).

References

Aas, M., Elvs shagen, T., Westlye, L. T., Kaufmann, T., Athanasiu, L., Djurovic, S., Ingrid Melle, Dennis van der Meer, Carmen Martin-Ruiz, Nils Eiel Steen, Ingrid Agartz, Andreassen, O. A. (2019). Telomere length is associated with childhood trauma in patients with severe mental disorders. Translational psychiatry, 9(1), 1-7.

Ahmad, S. A., Brito, D., Khalid, N., Ibrahim, M. A. (2020). Takotsubo cardiomyopathy. StatPearls. StatPearls Publishing, Florida.

Aubert, G., Lansdorp, P. M. (2008). Telomeres and aging. Physiological reviews, 88(2), 557-579.

Beserra, A. H. N., Kameda, P., Deslandes, A. C., Schuch, F. B., Laks, J., Moraes, H. S. D. (2018). Can physical exercise modulate cortisol level in subjects with depression? A systematic review and meta-analysis. Trends in psychiatry and psychotherapy, 40(4), 360-368.

Boonekamp, J. J., Bauch, C., Mulder, E., Verhulst, S. (2017). Does oxidative stress shorten telomeres?. Biology Letters, 13(5), 20170164.

Boss , S., Stalder, T., D`Antono, B. (2018). Childhood trauma, perceived stress, and hair cortisol in adults with and without cardiovascular disease. Psychosomatic Medicine, 80(4), 393.

Brouilette, S., Singh, R. K., Thompson, J. R., Goodall, A. H., Samani, N. J. (2003). White cell telomere length and risk of premature myocardial infarction. Arteriosclerosis, thrombosis, and vascular biology, 23(5), 842-846.

Brummett, B. H., Babyak, M. A., Singh, A., Jiang, R., Williams, R. B., Harris, K. M., Siegler, I. C. (2013). Socioeconomic indices as independent correlates of C-reactive protein in the National Longitudinal Study of Adolescent Health. Psychosomatic medicine, 75(9), 882.

Burke, H. M., Davis, M. C., Otte, C., Mohr, D. C. (2005). Depression and cortisol responses to psychological stress: a meta-analysis. Psychoneuroendocrinology, 30(9), 846-856.

Burke, H. M., Davis, M. C., Otte, C., Mohr, D. C. (2005). Depression and cortisol responses to psychological stress: a meta-analysis. Psychoneuroendocrinology, 30(9), 846-856.

Busch, L. Y., P ssel, P., Valentine, J. C. (2017). Meta-analyses of cardiovascular reactivity to rumination: A possible mechanism linking depression and hostility to cardiovascular disease. Psychological Bulletin, 143(12), 1378.

Ceccato, F., Lizzul, L., Barbot, M., Scaroni, C. (2020). Pituitary-adrenal axis and peripheral cortisol metabolism in obese patients. Endocrine, 69(2), 386-392.

Choi, J., Fauce, S. R., Effros, R. B. (2008). Reduced telomerase activity in human T lymphocytes exposed to cortisol. Brain, behavior, and immunity, 22(4), 600-605.

Cunha-Oliveira, T., Cristina Rego, A., R Oliveira, C. (2013). Oxidative stress and drugs of abuse: an update. Mini-Reviews in Organic Chemistry, 10(4), 321-334.

Dasanayaka, N. N., Sirisena, N., Samaranayake, N. (2020). The effects of meditation on length of telomeres in healthy individuals: A systematic review.

Dedovic, K., Duchesne, A., Andrews, J., Engert, V., Pruessner, J. C. (2009). The brain and the stress axis: the neural correlates of cortisol regulation in response to stress. Neuroimage, 47(3), 864-871.

Dekker, M. J. H. J., Koper, J. W., Van Aken, M. O., Pols, H. A. P., Hofman, A., De Jong, F. H., C. Kirschbaum, J. C. M. Witteman, Tiemeier, H. (2008). Salivary cortisol is related to atherosclerosis of carotid arteries. The Journal of Clinical Endocrinology Metabolism, 93(10), 3741-3747.

Denollet, J. (2005). DS14: standard assessment of negative affectivity, social inhibition, and Type D personality. Psychosomatic medicine, 67(1), 89-97.

Denollet, J., Vaes, J., Brutsaert, D. L. (2000). Inadequate response to treatment in coronary heart disease: adverse effects of type D personality and younger age on 5-year prognosis and quality of life. Circulation, 102(6), 630-635.

Ding, H., Chen, C., Shaffer, J. R., Liu, L., Xu, Y., Wang, X., ... Wang, D. W. (2012). Telomere length and risk of stroke in Chinese. Stroke, 43(3), 658-663.

Duffing, T. M., Greiner, S. G., Mathias, C. W., Dougherty, D. M. (2014). Stress, substance abuse, and addiction. Behavioral Neurobiology of Stress-related Disorders, 237-263.

Epel, E. S., Lin, J., Dhabhar, F. S., Wolkowitz, O. M., Puterman, E., Karan, L., Blackburn, E. H. (2010). Dynamics of telomerase activity in response to acute psychological stress. Brain, behavior, and immunity, 24(4), 531-539.

Espnes, G. A., Byrne, D. (2016). Type A behaviour and cardiovascular disease. In M. E. Alvarenga D. Byrne (Eds.), Handbook of psychocardiology (p. 645 664). Springer Science + Business Media.

Fiuza-Luces, C., Santos-Lozano, A., Joyner, M., Carrera-Bastos, P., Picazo, O., Zugaza, J. L., Lucia, A. (2018). Exercise benefits in cardiovascular disease: beyond attenuation of traditional risk factors. Nature Reviews Cardiology, 15(12), 731-743.

Friedman, M., Rosenman, R. H. (1959). Association of specific overt behavior pattern with blood and cardiovascular findings: blood cholesterol level, blood clotting time, incidence of arcus senilis, and clinical coronary artery disease. Journal of the American medical association, 169(12), 1286-1296.

Glei, D. A., Weinstein, M. (2019). Drug and alcohol abuse: the role of economic insecurity. American journal of health behavior, 43(4), 838-853.

Gu, H. F., Tang, C. K., Yang, Y. Z. (2012). Psychological stress, immune response, and atherosclerosis. Atherosclerosis, 223(1), 69-77.

Hartmann, N., Boehner, M., Groenen, F., Kalb, R. (2010). Telomere length of patients with major depression is shortened but independent from therapy and severity of the disease. Depression and anxiety, 27(12), 1111-1116.

Heistad, D. D., Wakisaka, Y., Miller, J., Chu, Y., Pena-Silva, R. (2009). Novel aspects of oxidative stress in cardiovascular diseases. Circulation Journal, 73(2), 201-207.

Herman, J. P., Ostrander, M. M., Mueller, N. K., Figueiredo, H. (2005). Limbic system mechanisms of stress regulation: hypothalamo-pituitary-adrenocortical axis. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 29(8), 1201-1213.

Hinkle Jr, L. E. (1973). The concept of" stress" in the biological and social sciences. Science, medicine and man, 1(1), 31-48.

Hoge, E. A., Bui, E., Palitz, S. A., Schwarz, N. R., Owens, M. E., Johnston, J. M., Simon, N. M. (2018). The effect of mindfulness meditation training on biological acute stress responses in generalized anxiety disorder. Psychiatry research, 262, 328-332.

Holsboer, F., Ising, M. (2010). Stress hormone regulation: biological role and translation into therapy. Annual review of psychology, 61, 81-109.

Hopf, D., Eckstein, M., Aguilar Raab, C., Warth, M., Ditzen, B. (2020). Neuroendocrine mechanisms of grief and bereavement: A systematic review and implications for future interventions. Journal of Neuroendocrinology, 32(8), e12887.

Hopf, D., Eckstein, M., Aguilar Raab, C., Warth, M., Ditzen, B. (2020). Neuroendocrine mechanisms of grief and bereavement: A systematic review and implications for future interventions. Journal of Neuroendocrinology, 32(8), e12887.

Horckmans, M., Bianchini, M., Santovito, D., Megens, R. T., Springael, J. Y., Negri, I., ... Steffens, S. (2018). Pericardial adipose tissue regulates granulopoiesis, fibrosis, and cardiac function after myocardial infarction. Circulation, 137(9), 948-960.

Jiang, Y., Da, W., Qiao, S., Zhang, Q., Li, X., Ivey, G., Zilioli, S. (2019). Basal cortisol, cortisol reactivity, and telomere length: A systematic review and meta-analysis. Psychoneuroendocrinology, 103, 163-172.

Jones, N. L., Gilman, S. E., Cheng, T. L., Drury, S. S., Hill, C. V., Geronimus, A. T. (2019). Life course approaches to the causes of health disparities. American Journal of Public Health, 109(S1), S48-S55.

Katakami, N. (2017). Mechanism of development of atherosclerosis and cardiovascular disease in diabetes mellitus. Journal of atherosclerosis and thrombosis, RV17014.

Kazufumi Nakamura ,Masato Murakami ,Daiji Miura ,Kei Yunoki ,Kenki Enko ,Masamichi Tanaka ,Yukihiro Saito ,Nobuhiro Nishii ,Toru Miyoshi ,Masashi Yoshida ,Hiroki Oe ,Norihisa Toh ,Satoshi Nagase ,Kunihisa Kohno ,Hiroshi Morita ,Hiromi Matsubara ,Kengo F Kusano ,Tohru Ohe, Hiroshi Ito. (2011). Beta-blockers and oxidative stress in patients with heart failure. MDPII Pharmaceuticals, 4(8), 1088-1100.

Kiecolt-Glaser, J. K., Glaser, R. (2002). Depression and immune function: central pathways to morbidity and mortality. Journal of psychosomatic research, 53(4), 873-876.

Komamura, K., Fukui, M., Iwasaku, T., Hirotani, S., Masuyama, T. (2014). Takotsubo cardiomyopathy: Pathophysiology, diagnosis and treatment. World Journal of Cardiology, 6(7), 602.

Kop, W. J., Gottdiener, J. S. (2005). The role of immune system parameters in the relationship between depression and coronary artery disease. Psychosomatic medicine, 67, S37-S41.

Kudielka, B. M., Kirschbaum, C. (2007). Biological bases of the stress response. In Stress and addiction (pp. 3-19). Academic Press.

Kumari, M., Shipley, M., Stafford, M., Kivimaki, M. (2011). Association of diurnal patterns in salivary cortisol with all-cause and cardiovascular mortality: findings from the Whitehall II study. The Journal of Clinical Endocrinology Metabolism, 96(5), 1478-1485.

Lazarus, R. S., Folkman, S. (1984). Stress, appraisal, and coping. Springer publishing company.

Lazzarino, A. I., Hamer, M., Stamatakis, E., Steptoe, A. (2013). Low socioeconomic status and psychological distress as synergistic predictors of mortality from stroke and coronary heart disease. Psychosomatic medicine, 75(3), 311.

LeBaron, T. W., Kura, B., Kalocayova, B., Tribulova, N., Slezak, J. (2019). A new approach for the prevention and treatment of cardiovascular disorders. Molecular hydrogen significantly reduces the effects of oxidative stress. Molecules, 24(11), 2076.

Leonard, B. E. (2001). The immune system, depression and the action of antidepressants. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 25(4), 767-780.

Lin, S. H., Lee, L. T., Yang, Y. K. (2014). Serotonin and mental disorders: a concise review on molecular neuroimaging evidence. Clinical Psychopharmacology and Neuroscience, 12(3), 196.

Manenschijn, L., Schaap, L., Van Schoor. N, van der Pas, S., Peeters. G, Lips. P, Koper. W, Van Rossum, E. F. C. (2013). High long-term cortisol levels, measured in scalp hair, are associated with a history of cardiovascular disease. The Journal of Clinical Endocrinology Metabolism, 98(5), 2078-2083.

Marketon, J. I. W., Glaser, R. (2008). Stress hormones and immune function. Cellular immunology, 252(1-2), 16-26.

Mart nez, P., Blasco, M. A. (2017). Telomere-driven diseases and telomere-targeting therapies. Journal of Cell Biology, 216(4), 875-887.

Marzilli, M., Merz, C. N. B., Boden, W. E., Bonow, R. O., Capozza, P. G., Chilian, W. M., Anthony N. DeMaria, Giacinta Guarini, Alda Huqi, Doralisa Morrone, Manesh R. Patel, Weintraub, W. S. (2012). Obstructive coronary atherosclerosis and ischemic heart disease: an elusive link!. Journal of the American College of Cardiology, 60(11), 951-956.

Masafi, S., Saadat, S. H., Tehranchi, K., Olya, R., Heidari, M., Malihialzackerini, S., ... Rajabi, E. (2018). Effect of stress, depression and type D personality on immune system in the incidence of coronary artery disease. Open access Macedonian journal of medical sciences, 6(8), 1533.

McEwen, B. S. (2003). Mood disorders and allostatic load. Biological psychiatry, 54(3), 200-207.

McLaren, L. (2007). Socioeconomic status and obesity. Epidemiologic reviews, 29(1), 29-48.

Mental Help. (2020). Medication Strategies for Stress Relief. American Addiction Centre. Retrieved from: https://www.mentalhelp.net/stress/reduction/medication

Milaniak, I., Jaffee, S. R. (2019). Childhood socioeconomic status and inflammation: a systematic review and meta-analysis. Brain, behaviour, and immunity, 78, 161-176.

Milosevic, I., McCabe, R. (2015). Phobias: The Psychology of Irrational Fear: The Psychology of Irrational Fear. ABC-CLIO.

Mitchell, C., McLanahan, S., Schneper, L., Garfinkel, I., Brooks-Gunn, J., Notterman, D. (2017). Father loss and child telomere length. Pediatrics, 140(2).

Moral, A. (2017). Guided meditation: A regimen for mental health. Indian Journal of Health and Wellbeing, 8(2), 180.

Morey, J. N., Boggero, I. A., Scott, A. B., Segerstrom, S. C. (2015). Current directions in stress and human immune function. Current opinion in psychology, 5, 13-17.

Morey, J. N., Boggero, I. A., Scott, A. B., Segerstrom, S. C. (2015). Current directions in stress and human immune function. Current opinion in psychology, 5, 13-17.

Morrison, R., O`Connor, R. C. (2005). Predicting psychological distress in college students: The role of rumination and stress. Journal of clinical psychology, 61(4), 447-460.

Needham, B. L., Smith, J. A., Zhao, W., Wang, X., Mukherjee, B., Kardia, S. L., Diez Roux, A. V. (2015). Life course socioeconomic status and DNA methylation in genes related to stress reactivity and inflammation: the multi-ethnic study of atherosclerosis. Epigenetics, 10(10), 958-969.

Newell-Price, J., Bertagna, X., Grossman, A. B., Nieman, L. K. (2006). Cushing`s syndrome. The Lancet, 367(9522), 1605-1617.

Nolen-Hoeksema, S. (2000). The role of rumination in depressive disorders and mixed anxiety/depressive symptoms. Journal of abnormal psychology, 109(3), 504.

Nykl ek, I., van Beugen, S., Denollet, J. (2013). Effects of mindfulness-based stress reduction on distressed (Type D) personality traits: a randomized controlled trial. Journal of Behavioral Medicine, 36(4), 361-370.

Petticrew, M. P., Lee, K., McKee, M. (2012). Type A behavior pattern and coronary heart disease: Philip Morris s crown jewel . American journal of public health, 102(11), 2018-2025.

Pollitt, R. A., Kaufman, J. S., Rose, K. M., Diez-Roux, A. V., Zeng, D., Heiss, G. (2007). Early-life and adult socioeconomic status and inflammatory risk markers in adulthood. European journal of epidemiology, 22(1), 55-66.

Psaltopoulou, T., Hatzis, G., Papageorgiou, N., Androulakis, E., Briasoulis, A., Tousoulis, D. (2017). Socioeconomic status and risk factors for cardiovascular disease: impact of dietary mediators. Hellenic journal of cardiology, 58(1), 32-42.

Puhlmann, L. M., Valk, S. L., Engert, V., Bernhardt, B. C., Lin, J., Epel, E. S., Vrti ka, P, Singer, T. (2019). Association of short-term change in leukocyte telomere length with cortical thickness and outcomes of mental training among healthy adults: a randomized clinical trial. JAMA network open, 2(9), e199687-e199687.

Puterman, E., Lin, J., Blackburn, E., O`donovan, A., Adler, N., Epel, E. (2010). The power of exercise: buffering the effect of chronic stress on telomere length. PloS one, 5(5), e10837.

Puterman, E., O Donovan, A., Adler, N. E., Tomiyama, A. J., Kemeny, M., Wolkowitz, O. M., Epel, E. (2011). Physical activity moderates stressor-induced rumination on cortisol reactivity. Psychosomatic medicine, 73(7), 604.

Reed, R. G., Raison, C. L. (2016). Stress and the immune system. In Environmental influences on the immune system (pp. 97-126). Springer, Vienna.

Rosenfeld, M. E., Campbell, L. A. (2011). Pathogens and atherosclerosis: update on the potential contribution of multiple infectious organisms to the pathogenesis of atherosclerosis. Thrombosis and haemostasis, 106(11), 858-867.

Sahoo, S., Padhy, S. K., Padhee, B., Singla, N., Sarkar, S. (2018). Role of personality in cardiovascular diseases: An issue that needs to be focused too!. Indian heart journal, 70, S471-S477.

Schiffer, A. A., Pavan, A., Pedersen, S. S., Gremigni, P., Sommaruga, M., Denollet, J. (2006). Type D personality and cardiovascular disease: Evidence and clinical implications. Minerva psichiatrica, 47(1), 79.

Schwartz, B. G., French, W. J., Mayeda, G. S., Burstein, S., Economides, C., Bhandari, A. K., Kloner, R. A. (2012). Emotional stressors trigger cardiovascular events. International Journal of Clinical Practice, 66(7), 631-639.

Sher, L. (2005). Type D personality: the heart, stress, and cortisol. Qjm, 98(5), 323-329.

Sies, H. (2000). What is oxidative stress?. In Oxidative stress and vascular disease (pp. 1-8). Springer, Boston, MA.

Simon, N. M., Smoller, J. W., McNamara, K. L., Maser, R. S., Zalta, A. K., Pollack, M. H., Wong, K. K. (2006). Telomere shortening and mood disorders: preliminary support for a chronic stress model of accelerated aging. Biological psychiatry, 60(5), 432-435.

Steptoe, A., Kivim ki, M. (2013). Stress and cardiovascular disease: an update on current knowledge. Annual review of public health, 34, 337-354.

Steven, S., Frenis, K., Oelze, M., Kalinovic, S., Kuntic, M., Bayo Jimenez, M. T., Ksenija Vujacic-Mirski, Johanna Helmst dter, Swenja Kr ller-Sch n, Thomas M nzel, Daiber, A. (2019). Vascular inflammation and oxidative stress: major triggers for cardiovascular disease. Oxidative medicine and cellular longevity, 2019.

Streblow, D. N., Orloff, S. L., Nelson, J. A. (2001). Do pathogens accelerate atherosclerosis?. The Journal of nutrition, 131(10), 2798S-2804S.

Thurston, R. C., Chang, Y., Barinas-Mitchell, E., von K nel, R., Jennings, J. R., Santoro, N., Matthews, K. A. (2017). Child abuse and neglect and subclinical cardiovascular disease among midlife women. Psychosomatic Medicine, 79(4), 441.

Vaiva, G., Ducrocq, F., Jezequel, K., Averland, B., Lestavel, P., Brunet, A., Marmar, C. R. (2003). Immediate treatment with propranolol decreases posttraumatic stress disorder two months after trauma. Biological psychiatry, 54(9), 947-949.

Vehmeijer, F. O., Santos, S., Gaillard, R., de Rijke, Y. B., Voortman, T., van den Akker, E. L., Janine F Felix, Elisabeth F C van Rossum, Jaddoe, V. W. (2021). Associations of hair cortisol concentrations with general and organ fat measures in childhood. The Journal of Clinical Endocrinology Metabolism, 106(2), e551-e561.

Vogelzangs, N., Beekman, A. T., Milaneschi, Y., Bandinelli, S., Ferrucci, L., Penninx, B. W. (2010). Urinary cortisol and six-year risk of all-cause and cardiovascular mortality. The Journal of Clinical Endocrinology Metabolism, 95(11), 4959-4964.

Walker, B. R., Best, R., Shackleton, C. H., Padfield, P. L., Edwards, C. R. (1996). Increased vasoconstrictor sensitivity to glucocorticoids in essential hypertension. Hypertension, 27(2), 190-196.

Wei, L., MacDonald, T. M., Walker, B. R. (2004). Taking glucocorticoids by prescri ption is associated with subsequent cardiovascular disease. Annals of internal medicine, 141(10), 764-770.

Weischer, M., Bojesen, S. E., Cawthon, R. M., Freiberg, J. J., Tybj rg-Hansen, A., Nordestgaard, B. G. (2012). Short telomere length, myocardial infarction, ischemic heart disease, and early death. Arteriosclerosis, thrombosis, and vascular biology, 32(3), 822-829.

Whitworth, J. A., Williamson, P. M., Mangos, G., Kelly, J. J. (2005). Cardiovascular consequences of cortisol excess. Vascular health and risk management, 1(4), 291.

Willeit, P., Willeit, J., Brandsta tter, A., Ehrlenbach, S., Mayr, A., Gasperi, A., Siegfried Weger, Friedrich Oberhollenzer, Markus Reindl, Florian Kronenberg, Kiechl, S. (2010). Cellular aging reflected by leukocyte telomere length predicts advanced atherosclerosis and cardiovascular disease risk. Arteriosclerosis, thrombosis, and vascular biology, 30(8), 1649-1656.

World Health Organisation. (2017). Cardiovascular Diseases (CVDs): Key Facts and Risk Factors. Retrieved from: https://www.who.int/news-room/fact-sheets/detail/cardiovascular-diseases-(cvds)

Yegorov, Y. E., Poznyak, A. V., Nikiforov, N. G., Starodubova, A. V., Orekhov, A. N. (2021). Role of Telomeres Shortening in Atherogenesis: An Overview. Cells, 10(2), 395.

Zhang, Y. B., Chen, C., Pan, X. F., Guo, J., Li, Y., Franco, O. H., Liu, G, Pan, A. (2021). Associations of healthy lifestyle and socioeconomic status with mortality and incident cardiovascular disease: two prospective cohort studies. bmj, 373.