Diagnosing Cardiovascular Disease From the Perspective of the Brain and Inflammation
Numerous lifestyle, emotional, and biological factors have been identified as risk factors for heart disease. These include socioeconomic status, early childhood and intimate partner abuse, disruption of sleep patterns, lack of exercise, and unhealthy food choices. Genetic and epigenetic factors are also critical components of the equation. A common denominator that links directly or indirectly all of these factors is inflammation. In some instances, the production of inflammatory molecules may precipitate the illness, while in others they may be produced in response to the underlying cause. Regardless of whether through direct or indirect means, inflammation contributes to the gradual loss of cellular energy substrates, which?culminates in impaired diastolic performance. For that reason, to refer to a failure of the cardiovascular system as heart or cardiovascular disease lessens the potentially important contribution of a myriad of other factors. This article begins with the premise that impaired cardiac functioning is more than a heart disorder. An argument will be made that impaired cardiac functioning can also be an economic, behavioral, and/or emotional disorder, which subsequently gives rise to a metabolic failure. Therefore, a multisystems approach should be taken to identify prior to the onset of damage biological and nonbiological predictors of impending heart disease. (Altern Ther Health Med. 2013;19(suppl 1):8-9.)
Nicholas R. S. Hall, PhD, directs the Center for Psychoneuroimmunology at the University of South Florida College of Nursing, Tampa, Florida.
Corresponding author: Nicholas R. S. Hall, PhD
The association of inflammation with heart disease is well established, with the measurement of the high sensitive C-reactive protein (hs-CRP) often included in screenings.1,2 Further evidence for a link between inflammation and heart disease is the recognition that both chronic low grade inflammation as well as acute episodes precipitated by viral infection can increase the risk of cardiovascular events.3 A commonly embraced interpretation is that inflammatory processes directly erode endothelial cells lining blood vessels. Then, chemotactic agents produced by injured endothelial cells modify blood lipids, particularly low-density lipoproteins (LDLs). These become oxidized, causing further damage to adjacent cells in the expanding inflammatory environment. Macrophages transform into lipid containing foam cells, thus setting the initial stage of atheroma development. In addition to hs-CRP, the proinflammatory cytokines, interleukin-6, tumor necrosis factor-?, and tumor necrosis factor-??s soluble receptors have also been correlated with the progression of heart failure.4
Yet, despite the widely accepted link between inflammation and heart disease, the assessment of a growing number of especially psychosocial inflammation modifiers have yet to be included in a systematic manner while assessing a person?s risk for heart disease. This is despite growing evidence that the effects of inflammation upon the heart may be via the ability of proinflammatory cytokines to alter the activity of neurons in brain regions capable of mediating both the heart and mood.5 Thus, changes in affect may well be a harbinger of impending heart disease, especially in those individuals with various psychosocial risk factors. Alteration of autonomic nervous system pathways and cardiac centers regulating heart rate variability can be directly influenced by inflammation. Depressed mood is both a risk factor for heart disease and also a common consequence of inflammation. In addition, some of the same brain regions linked with cardiac regulation and mood are also associated with cognitive processing.6 Therefore, combining measures of a person?s psychological well-being with biological markers may greatly enhance the probability of detecting heart disease prior to a systolic event. A number of psychosocial factors are candidates for inclusion in such a panel.
A risk factor for heart disease that has emerged in recent years is a propensity for psychological distress, which has been designated the type D or distressed personality type.7 It is characterized by social inhibition and a high level of negative affect. In patients with heart failure, the type D personality has been found associated with higher levels of tumor necrosis factor-? along with its soluble receptors.8 This observation is consistent with many other studies linking measures of emotional distress with inflammation. Since the mid-1960s, an association between rheumatoid arthritis and personality has been reported.9 George Solomon, the founder of the modern era of psychoneuroimmunology, reported that despite having grown up in the same household and being exposed to the same lifestyle, it was not uncommon for one identical twin to present with the symptoms of arthritis while the other was free of this disease. It was consistently observed that the vulnerable twin invariably exhibited the ?rheumatoid arthritic personality.? The defining characteristic of this individual was a propensity for accommodation and tending to the emotional needs of others instead of their own?a person who says ?yes? when they want to say ?no.? Later, this personality was carefully scrutinized and designated the type C coping style.10 It is characterized by a failure to acknowledge and express emotional cues, as well as a propensity to focus upon the needs of others. In addition to the association with inflammation, the type C style is correlated with an increased risk of developing certain forms of cancer, especially malignant melanoma, hence, the designation type C or cancer-prone.10 However, it might be more accurate to define such individuals as being prone to inflammation. Indeed, the type C style is associated with elevated levels of the proinflammatory cytokine, IL-6.11 However, identifying the association between heart disease and psychological factors will not be easy.
While emotional distress has clearly been identified as a risk factor for heart disease, it may not have occurred during the recent history of the patient, nor necessarily during their lifetime. Growing up in a low socioeconomic status environment has been linked with not only elevated LDL and reduced HDL, but an increased incidence of both stroke12 and heart disease.13 The fact it was the early exposure to an uncertain environment and not the current context was revealed in a study of medical school graduates, all of whom enjoyed a high socioeconomic lifestyle at the time of the study. Yet those who grew up under impoverished circumstances were more likely to develop cardiovascular disease prior to the age of 50.14 Another team of investigators has reported that the parent?s environmental circumstances can influence the systolic blood pressure and CRP levels of their children. Schreier and Chen15 found that if the parent?s childhood was spent in a low socioeconomic environment, their children would have higher CRP and systolic blood pressure compared with parents who were raised under more affluent circumstances. This finding was independent of the child?s current circumstances. Therefore, a consideration of intergenerational factors may have utility when predicting those at risk of cardiovascular disease.
Suspicion of heart disease may be raised by a report of fatigue. While it can certainly be a consequence of reduced cardiac output, the fatigue may also be occurring independent of heart disease, yet be indicative of inflammation. Early life stress associated with not just poverty, but with childhood abuse, can be correlated with both increased inflammation16 and fatigue and chronic fatigue syndrome in adulthood.17 Because fatigue as well as sleep disturbances are part of the behavioral consequences of inflammation referred to as ?sickness behavior,? it has long been assumed that these and other components of sickness behavior are due to pro-inflammatory cytokines acting within the central nervous system.18 Perhaps it is time to expand the assessment of heart disease by adopting the same multisystems approach that has defined the field of psychoneuroimmunology. Some of the missing pieces to the cardiovascular puzzle may well be lurking in the brain instead of the heart.
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