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.

Objectives Despite nearly 40 years of research, the role of plasma triglyceride as a risk factor for cardiovascular disease remains elusive. The objectives of the present study were to quantify the...

Plasma triglyceride level is a risk factor for cardiovascular disease independent of high-density lipoprotein cholesterol level: a meta-analysis of population-based prospective studies.

Background— Many epidemiological studies have reported on associations between serum triglyceride concentrations and the risk of coronary heart disease, but this association has not been reliably quantified. In the present study, we report 2 separate nested case-control comparisons in 2 different prospective, population-based cohorts, plus an updated meta-analysis of 27 additional prospective studies in general Western populations. Methods and Results— Measurements were made in a total of 3582 incident cases of fatal and nonfatal coronary heart disease and 6175 controls selected from among the 44 237 men and women screened in the Reykjavik and the European Prospective Investigation of Cancer (EPIC)-Norfolk studies. Repeat measurements were obtained an average of 4 years apart in 1933 participants in the EPIC-Norfolk Study and an average of 12 years apart in 379 participants in the Reykjavik study. The long-term stability of log-triglyceride values (within-person correlation coefficients of 0.64 [95% CI, 0...

Triglycerides and the Risk of Coronary Heart Disease 10 158 Incident Cases Among 262 525 Participants in 29 Western Prospective Studies

Felton & Cole (1963) estimate that all cardiovascular diseases accounted for 12 per cent of the time lost by the ‘working population’ in the US, for a total economic loss of about $4 billion in a single year. A report (1969) by the Department of Health and Social Security in the UK shows, as Aldridge (1970) indicates, that the sum of incapacity for men suffering from mental, psychoneurotic and personality disorders, nervousness, debility and migraine headache accounted for 22·8 million work days lost in 1968 alone (second only to bronchitis in the league table of illness and lost working days). Coronary heart disease and mental ill health together, therefore, represent a serious cost for industry both in human and financial terms.

Occupational sources of stress: a review of the literature relating to coronary heart disease and mental ill health

Depression as a predictor for coronary heart disease. a review and meta-analysis

Clinical coronary heart disease (CHD) occurred in 257 subjects during eight to nine years of follow-up (average, 8 1/2 years) in a prospective study of 39- to 59-year-old employed men. Incidence of CHD was significantly associated with parental CHD history, reported diabetes, schooling, smoking habits, overt behavior pattern, blood pressure, and serum levels of cholesterol, triglyceride, and β-lipoproteins. The type A behavior pattern was strongly related to the CHD incidence, and this association could not be explained by association of behavior pattern with any single predictive risk factor or with any combination of them. ( JAMA 233:872-877, 1975)

https://jamanetwork.com/HttpHandlers/ArticlePdfHandler.ashx?journal=jama&articleId=337636&pdfFileName=jama_233_8_016.pdf

Coronary heart disease in the Western collaborative group study. A follow-up experience of two years.

The possible involvement of a specific overt behaviour pattern in the pathogenesis of clinical coronary heart disease (CHD) has been under careful study. The characteristics of this overt behaviour pattern, called Behaviour Pattern A, have been described previously (Friedman and Rosenman, 1959). In brief, it is 6haracterized by extremes of competitiveness, striving for achievement, aggressiveness (yet sometimes stringently repressed), haste, impatience, restlessness, hyper-alertness, explosiveness of speech, tenseness of facial musculature, and feelings of being under the pressure of time and under the challenge of responsibility. In an earlier study this pattern was found to be associated with increased prevalence of CHD, Rosenman, Friedman, Straus, Wurm, Kositchek, Hahn, and Werthessen (1964). To test this finding more decisively, a collaborative prospective study of CHD was initiated in 1960-61 among 3,524 men aged 39-59 years. At the end of a mean follow-up period of 21 years, subjects classified at intake as having exhibited Pattern A showed a considerably higher incidence of new CHD than those classified prospectively as exhibiting the converse Pattern B (Rosenman, Friedman, Straus, Wurm, Jenkins, and Messinger, 1966). It therefore appeared important to the investigators to examine the adequacy of their technique for differentiating Pattern A from Pattern B. The current study tests the reliability of assessment of the behaviour patterns, both in terms of agreement between judges and stability of the rating over time. The behaviour pattern was assessed by means of an oral interview designed especially for this purpose. Detection of Behaviour Pattern A consists in determining whether a subject is in active and continuous conflict either with other subjects or with time. This condition reveals itself through various

https://jech.bmj.com/content/jech/22/1/16.full.pdf

Replicability of rating the coronary-prone behaviour pattern.

The occurrence of new coronary heart disease (CHD) in the presence of below average serum levels of lipids and lipoproteins was studied during a 4 1/2-year period of observation of 2,998 normotensive men, aged 39 to 59 years at intake into a prospective, epidemiological investigation. It was found from this study that the normotensive, middle-aged man with the fully developed type B behavior pattern was essentially immune to the development of clinical CHD if he exhibited a serum cholesterol level less than 226 mg/100 ml, a serum triglyceride level less than 126 mg/100 ml, or a serum β-/α-lipoprotein ratio less than 2.01, singly or in combination.

C D Jenkins

Papers

Coronary heart disease in the Western collaborative group study. A follow-up experience of two years.

Replicability of rating the coronary-prone behaviour pattern.

The Prediction of Immunity to Coronary Heart Disease

Is there a coronary-prone personality?