Recent studies provide clear and convincing evidence that psychosocial factors contribute significantly to the pathogenesis and expression of coronary artery disease (CAD). This evidence is composed largely of data relating CAD risk to 5 specific psychosocial domains: (1) depression, (2) anxiety, (3) personality factors and character traits, (4) social isolation, and (5) chronic life stress. Pathophysiological mechanisms underlying the relationship between these entities and CAD can be divided into behavioral mechanisms, whereby psychosocial conditions contribute to a higher frequency of adverse health behaviors, such as poor diet and smoking, and direct pathophysiological mechanisms, such as neuroendocrine and platelet activation. An extensive body of evidence from animal models (especially the cynomolgus monkey, Macaca fascicularis) reveals that chronic psychosocial stress can lead, probably via a mechanism involving excessive sympathetic nervous system activation, to exacerbation of coronary artery atherosclerosis as well as to transient endothelial dysfunction and even necrosis. Evidence from monkeys also indicates that psychosocial stress reliably induces ovarian dysfunction, hypercortisolemia, and excessive adrenergic activation in premenopausal females, leading to accelerated atherosclerosis. Also reviewed are data relating CAD to acute stress and individual differences in sympathetic nervous system responsivity. New technologies and research from animal models demonstrate that acute stress triggers myocardial ischemia, promotes arrhythmogenesis, stimulates platelet function, and increases blood viscosity through hemoconcentration. In the presence of underlying atherosclerosis (eg, in CAD patients), acute stress also causes coronary vasoconstriction. Recent data indicate that the foregoing effects result, at least in part, from the endothelial dysfunction and injury induced by acute stress. Hyperresponsivity of the sympathetic nervous system, manifested by exaggerated heart rate and blood pressure responses to psychological stimuli, is an intrinsic characteristic among some individuals. Current data link sympathetic nervous system hyperresponsivity to accelerated development of carotid atherosclerosis in human subjects and to exacerbated coronary and carotid atherosclerosis in monkeys. Thus far, intervention trials designed to reduce psychosocial stress have been limited in size and number. Specific suggestions to improve the assessment of behavioral interventions include more complete delineation of the physiological mechanisms by which such interventions might work; increased use of new, more convenient "alternative" end points for behavioral intervention trials; development of specifically targeted behavioral interventions (based on profiling of patient factors); and evaluation of previously developed models of predicting behavioral change. The importance of maximizing the efficacy of behavioral interventions is underscored by the recognition that psychosocial stresses tend to cluster together. When they do so, the resultant risk for cardiac events is often substantially elevated, equaling that associated with previously established risk factors for CAD, such as hypertension and hypercholesterolemia.

Impact of psychological factors on the pathogenesis of cardiovascular disease and implications for therapy.

Twenty-four hour time domain heart rate variability and heart rate: relations to age and gender over nine decades.

This review investigates the association between positive psychological well-being (PPWB) and cardiovascular disease (CVD). We also consider the mechanisms by which PPWB may be linked with CVD, focusing on the health behaviors (e.g., smoking, alcohol consumption, physical activity, sleep quality and quantity, and food consumption) and biological functions (e.g., cardiovascular, inflammatory, and metabolic processes) that are most relevant for cardiovascular health. Because PPWB is a broad concept, not all aspects of PPWB may be associated with cardiovascular health. Thus, we distinguish between eudaimonic well-being, hedonic well-being, optimism, and other measures of well-being when reviewing the literature. Findings suggest that PPWB protects consistently against CVD, independently of traditional risk factors and ill-being. Specifically, optimism is most robustly associated with a reduced risk of cardiovascular events. In general, PPWB is also positively associated with restorative health behaviors and biological function and inversely associated with deteriorative health behaviors and biological function. Cardiovascular health is more consistently associated with optimism and hedonic well-being than with eudaimonic well-being, although this could be due in part to more limited evidence being available concerning eudaimonic well-being. Some similarities were also evident across different measures of PPWB, which is likely due to measurement overlap. A theoretical context for this research is provided, and suggestions for future research are given, including the need for additional prospective investigations and research that includes multiple constructs of psychological well-being and ill-being.

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The Heart's Content: The Association Between Positive Psychological Well-Being and Cardiovascular Health

Reduced heart rate variability carries an adverse prognosis in patients who have survived an acute myocardial infarction This article reviews the physiology, technical problems of assessment, and clinical relevance of heart rate variability The sympathovagal influence and the clinical assessment of heart rate variability are discussed Methods measuring heart rate variability are classified into four groups, and the advantages and disadvantages of each group are described Concentration is on risk stratification of postmyocardial infarction patients The evidence suggests that heart rate variability is the single most important predictor of those patients who are at high risk of sudden death or serious ventricular arrhythmias

https://onlinelibrary.wiley.com/doi/pdf/10.1002/clc.4960130811

Heart rate variability

We have suggested that among conscious dogs with a healed anterior wall myocardial infarction (MI) a depressed baroreflex sensitivity (BRS) carries a higher risk of developing ventricular fibrillation during a brief ischemic episode associated with an exercise stress test. The clinical and pathophysiological implications of our previous findings prompted the present study, which addressed three major questions: 1) Is, indeed, analysis of BRS after MI a specific and sensitive marker for sudden death-risk stratification? 2) Does MI modify BRS? 3) Does analysis of BRS before MI provide information about outcome during ischemic episodes occurring after MI? An anterior MI was produced in 301 dogs, and 4 weeks later, a 2-minute circumflex coronary artery occlusion beginning during the last minute of an exercise stress test could be performed in 192 animals. Ventricular fibrillation occurred in 106 (55%) dogs (susceptible to sudden death), whereas 86 (45%) dogs (resistant to sudden death) survived. BRS was assessed by the phenylephrine method and was expressed by the regression line relating RR intervals to blood-pressure changes. BRS was significantly lower among susceptible than among resistant dogs (9.1 +/- 6.0 vs. 17.7 +/- 6.5 msec/mm Hg, p less than 0.0001). The risk for sudden death increased from 20% (15 of 73 dogs) for a BRS greater than 15 msec/mm Hg to 91% (62 of 68 dogs) for a BRS less than 9 msec/mm Hg (p less than 0.001). An internal control study in 55 animals showed that BRS was reduced 4 weeks after MI compared with control conditions (13.5 +/- 6.7 vs. 17.8 +/- 6.6 msec/mm Hg, p less than 0.001) and that a reduction occurred in 73% of animals. Susceptible dogs and those that spontaneously died after MI had a lower BRS even before the MI (16.2 +/- 5.9 vs. 22.2 +/- 6.2 msec/mm Hg, p less than 0.001). The risk for sudden death after MI increased from 35% (nine of 26 dogs) for a BRS before MI greater than 20 msec/mm Hg to 85% (17 of 20 dogs) for a BRS before MI less than 14 msec/mm Hg (p less than 0.001). This study demonstrates that the presence of a reduced BRS is associated with a greater susceptibility to ventricular fibrillation during subsequent ischemic episodes. In the majority of dogs, BRS is reduced after an MI. The results in 192 conscious dogs with a healed MI indicate that analysis of BRS is a powerful tool for risk stratification not only after, but even before, the occurrence of an MI.

Autonomic mechanisms and sudden death. New insights from analysis of baroreceptor reflexes in conscious dogs with and without a myocardial infarction.

Data are analyzed from 5 patients who died suddenly during ambulatory electrocardiographic monitoring. Three of the patients were also assessed in terms of 2 recently developed indexes of heart rate (HR) variability. One of these, the standard deviation of RR intervals during successive 5-minute segments averaged over 24 hours, has been reported to be a putative index of vagal tone. Comparisons were made with HR variability findings in 20 normal volunteers. Sudden death was due to ventricular tachycardia degenerating into ventricular fibrillation in all cases. Both early (3 patients) and late cycle (2 patients) ventricular premature complexes initiated the terminal dysrhythmia. An increased density of ventricular ectopic activity was noted in the hour before onset of ventricular fibrillation. HR variability as measured by the standard deviation was significantly (p

Glenn A. Myers

Papers

Heart rate variability and sudden death secondary to coronary artery disease during ambulatory electrocardiographic monitoring

Heart rate variability in sudden cardiac death.

Active boundary conditions for modeling propagating cardiac action potentials.