Lipids in psychological research: the last decade.

Biological Psychology 34 (1992) l-43 0 1992 Elsevier Science Publishers B.V. All rights reserved

0301-0511/92/%05.00

Lipids in psychological research: The last decade Raymond Niaura, Catherine M. Stoney and Peter N. Herbert The Miriam Hospital/Brown

University School of Medicine, Providence, RI, USA

We review the recent literature examining lipid changes during stressful experiences, and the psychological and constitutional differences that influence lipid levels at rest and that may modulate lipid response to stress. Mild forms of chronic or episodic stress are apparently not associated with alterations in lipids and lipoproteins, but severe forms of real or perceived stress do appear to alter lipid levels. Acute laboratory stress is frequently associated with short-term alterations in lipids and lipoproteins, but the significance of these changes is unclear. Several individual characteristics, such as heightened neuroendocrine or autonomic reactivity to stressors, Type A component behavior, and other aspects of personality, appear to be associated with an atherogenic lipid profile. Stress may influence lipid concentrations and metabolism through a variety of physiological and behavioral mechanisms, but none have been clearly elucidated. Future research should concentrate on understanding these mechanisms. Keywords:

Stress,

lipids, lipoproteins,

Lipids in psychological

cholesterol,

psychophysiology,

Type A, emotional

arousal

research: the last decade

In 1982, Dimsdale and Herd reviewed 60 studies which examined the effects of emotional arousal on plasma lipids (Dimsdale & Herd, 1982). They concluded that: (a) free fatty acids (FFA) are almost always elevated during psychologically stressful events; (b) most studies show an increase in total cholesterol above baseline under stressful conditions; and (c) there is no consistent pattern of triglyceride response to stressors. They also lamented that this topic had been relatively ignored recently, despite a considerable amount of research activity which occurred 20 years before the review was published. Finally, they called for further research in this area, citing advances in techniques for measuring stress, neuroendocrine response and lipid metabolism which would promise to elucidate further the causes and mechanisms that govern the relationship between stress and lipids. Because of the paucity of data available at that time, and despite the fact that a number of individual difference variables have been implicated in the pathogenesis of CHD (Manuck, Kaplan & Matthews, 1986), Dimsdale and Herd specifically Correspondence to: Raymond Hospital, 164 Summit Avenue,

Niaura, Ph.D., Division of Behavioral Providence, RI 02906, USA.

Medicine,

The

Miriam

2

R. Niaura et al. / Lipids in psychological research

chose not to examine the influence of other psychological factors on lipids. Ten years later, we are in a position to resurvey the scientific literature, and to determine whether Dimsdale and Herd’s conclusions still hold; whether their recommendations for future research have been followed; and whether we are now in a position to begin examining the influence of other psychological characteristics on lipid levels and metabolism.

Why study lipids in psychological

research?

There is little doubt that total cholesterol and its major constituents, low density lipoprotein (LDL) cholesterol and high density lipoprotein (HDL) cholesterol, are strongly related to the risk of developing atherosclerotic diseases of arteries with damage to end organs such as the kidney, brain and heart. The relationship between total cholesterol and CHD in particular appears to be graded and continuous, suggesting that there may be no optimal cutpoint for identifying high risk groups (Stamler, Wentworth & Neaton, 1986). Furthermore, intervention trials have convincingly demonstrated that reductions in total and LDL cholesterol significantly decrease risk for coronary morbidity and mortality (LRC-CPPT, 1984; Manninen et al., 1988). Similarly, trials that have primarily resulted in HDL cholesterol increases and, to a lesser extent, LDL cholesterol decreases, have also resulted in reductions in CHD risk (Frick et al., 1987). We know that levels of circulating lipids and lipoproteins are influenced to a large degree by genetic and homeostatic mechanisms which regulate lipid metabolism (Breslow, 19911, by dietary factors such as consumption of saturated fats and alcohol (Arntzenius et al., 1985; Castelli, Doyle, Gordon et al., 19771, and by behavioral factors such as exercise and smoking (Hulley, Cohen & Widdowson, 1977; Wood et al., 1976). Yet, combined, these factors still cannot account for more than a fraction of the variability in lipids and lipoproteins. The substantial inter- and intra-individual variation in lipid levels suggests that psychological factors may contribute to the determination of lipid and lipoprotein levels, both between and within individuals. Further delineation of the factors which influence metabolism of lipids and lipoproteins may have direct relevance to increasing our understanding of the pathogenesis of cardiovascular disease. In the first section of this paper, we review research concerning stress and lipids over the past 10 years. We pay particular attention to studies which have examined the response to real-world stressors and to those studies which have examined lipid and lipoprotein correlates of reactivity to laboratory stressors. In the subsequent section, we discuss studies published in the last 3.5 years concerning the role that individual differences in psychological characteristics may play in lipid metabolism. More specifically, we examine

R. Niaura et al. / Lipids in psychological

research

3

the influence of Type A behavior and its subcomponents; personality, coping style and mood; and social support on lipid levels. In this section, we also examine the role that individual differences in constitutional factors (gender, elevated risk for CHD) may play in interacting with stress to effect changes in lipid and lipoprotein levels. In the final section, we propose a model for some of the behavioral and physiological mechanisms which may link psychological factors and the experience of stress to alterations in lipid concentration and metabolism. and we offer some recommendations for further research.

Stress and lipids

Here, we review research studies investigating stress and lipids which have appeared in published form over the past 10 years. First, we confine our review to studies that have examined the human response to naturally occurring stressors which are episodic in nature. Episodic stressors are considered to be those circumstances in which stress is experienced for more than a few hours, although not usually for more than a few weeks, and which are likely to recur periodically. Academic examinations or temporary periods of high occupational workload exemplify episodic stressors. Second, we review studies of chronic stress. Chronic stressors are considered to be those circumstances in which stress is experienced more or less at a constant level over a period of time ranging from a few weeks to years. Long-term job strain or unemployment exemplify chronic stressors. Studies of episodic and chronic stress are particularly important, for they serve to establish the real-world relevance of, and the meaningful boundaries for, the stress-lipid relationship. Finally, we consider studies which have examined the lipid response to acute, laboratory stressors. Studies such as these have an advantage over studies of real-life stressors, because they are able to be tightly controlled and they provide some insight into putative physiological mechanisms involved in mobilizing serum lipids and lipoproteins and, potentially, the pathogenesis of atherosclerosis. Relevant reports published since 1981 in peer-reviewed journals were collected by searching computerized data bases (MEDLINE and PSYCH ABSTRACTS), reference lists of published articles, and by actively scanning current issues of medical and psychological journals. The computer searches included the keywords stress, emotion, lipids and lipoproteins. Studies were included in the review if they provided some direct estimate of the degree of association between a stressor or subjectively perceived stress and serum lipids and/or lipoproteins, and if they were published in English. Studies were included which focused primarily on the effects of psychological and behavioral stressors on humans. We excluded studies in which the stressor may have produced psychological changes but where the nature of the

subjects

Within

et al. (1990)

McCann

Female medical students (N=9) Grants and contracts service workers t N = 14)

(N

of grant

Within

et al. (1984)

Kirkeby

patients

Processing university applications

subjects

Within

surgery

Dental = 21)

Goldstein

(N = 118)

Increase

total

cholesterol. No changes in total, LDL, HDL, VLDL cholesterol and subfractions or triglycerides.

in

subjects

Within

Notification of selection for military line command Baseline to preop waiting period of several days Examinations

students

Officer

Gill et al. (1985)

(N = 26)

in total, LDL cholesterol or

subjects

Within

Examinations

students

Medical

Flynn et al. (1984)

No change and HDL triglycerides.

subjects

Within

Examinations

students

Medical

Bijlani et al. (1986)

et al. (19821

Within/between subjects

Examinations

students (n = 8) controls (n = 7)

Medical Matched

Biilani et al. (1983)

subjects

Increase in total, LDL, and HDL cholesterol only in medical students. Increase in total, LDL, and HDL cholesterol only in medical students during October exam. No change in total, LDL, HDL cholesterol during December examinations. No change in total and HDL cholesterol. Possible diet and stress interaction for triglycerides. Increase in total cholesterol. No change in HDL. Within/between subjects

Examinations

(N = 5)

Results

Design

Stressor (n = 8)

students (n = 8)

Medical Controls

Authors

Subjects

stressors

(yr)

Table 1 Studies of episodic

P

P

et al. (1987)

Smoak et al. (1990)

Pincomb

(1983)

Orth-Comer

al.

et al. (1987)

et al. (1991)

et

O’Donnell

Niaura

Netterstrom (1988)

students (n = 12)

Medical Controls

(N = 20)

(N = 44)

students

Navy trainees

Medical

(n = 13)

(N = 16)

(N = 24)

Con-

= 35) (n = = 12)

(N = 45)

students

Medical

Police officers

students

Medical

Medical students (N divided into stressed 23) and unstressed (n groups. Accountants (n = 20) trols (n = 20)

subjects

subjects

Within

Within

Clockwise vs. counter-clockwise Shift rotation

Hell week

subjects


Examinations

Within

subjects

Within

Examinations

Examinations

subjects

Within



Examinations

Tax season

Examinations

No within- or between-subject effects for total, LDL, HDL cholesterol and subfractions, triglycerides or apolipoproteins. No changes for total, LDL, HDL cholesterol and subfractions, triglycerides or apolipoproteins. No changes for total and LDL cholesterol, triglycerides or apolipoproteins. Increase in HDL and HDL,. Increase in total and LDL cholesterol within students but not controls. No effects on VLDL, triglyceride or HDL subfractions. Increase in triglycerides but no change in total cholesterol due to counter-clockwise shift rotation. No change in total and HDL cholesterol or triglycerides. Decrease in free fatty acids. Decrease in total and LDL cholesterol, increase in HDL.

No within- or between-subject effects on total cholesterol.

van Doornen et al. (1989) van Doornen and van Blokland (1987)

et al. (1986)

(yr)

1 (continued)

Trevisan

Authors

Table

52)

students

(N =

Examinations

Within

subjects

subjects

Within

Thesis defense

candidates

Doctoral

(N =

Increase in total cholesterol and triglycerides within exposed but not within control subjects. No change in total cholesterol. Increase in total cholesterol. Within/between subjects

Earthquake

Exposed exposed workers

33) University

Results

Design

Stressor (n = 96) and non(n = 96) factory

Subjects


7

stressor was primarily physiological (e.g. surgery, cold, starvation, exercise, myocardial infarction, or other acute illness). We also excluded studies in which stress hormones (e.g. epinephrine) were administered directly to subjects. Tables 1-3 present the results of our search. Sixty-two published studies were identified in this manner. Episodic stressors

It is apparent that most studies of episodic stress have focused on examination stressors, and that medical students remain the favored subjects of study (Bijlani, Gandhi & Tandon, 1983; Bijlani, Sud, Gandhi & Tandon, 1986; Flynn et al., 1984; Kirkeby, Risiie & Kirkeby, 1984; Netterstrom, Danborg & Olesen, 1988; Niaura et al., 1991; O’Donnell et al., 1987; Pincomb, Lovallo, Passey, Bracket & Wilson, 1987). This is understandable, because students progress as cohorts through a homogeneous experience, the examination period, which is clearly time linked and possesses face validity as a stressor, thus strengthening any inferences about stress effects on lipids. Next most frequently studied have been stressors which occur mostly within the context of occupational demands, e.g. military training exercises (Smoak Norton, Ferguson & Deuster, 19901, military assignment (Gill et al., 1985) and workload increases (McCann, Wamick & Knapp, 1990). Finally, one study (Trevisan et al., 1986) serendipitously was able to study the effects of a natural disaster, an earthquake, on serum lipids because a lipoprotein surveillance program was under way before and after the earthquake struck. Again, these studies capitalize on the discrete nature of the stressors and the unequivocal “stressfulness” of the circumstances. Upon examining the results of these investigations, the overall conclusion is akin to the debate about the glass being half-full or half-empty. While there is some positive support for a relationship, several studies have yielded either null results or results which are opposite in direction to those which might be expected (Table 1). Of the positive studies, the most common finding is an increase in the level of total cholesterol, with fewer studies finding a corresponding increase in LDL cholesterol. No studies noted a decrease in HDL, in fact, some studies found that HDL increased in response to stress (e.g. Bijlani et al., 1983; 1986; Smoak et al., 1990). This finding suggests that a common mechanism is responsible for the simultaneous elevations in both LDL and HDL cholesterol. Very few studies examined effects of stressors on apolipoproteins, and no positive findings have been noted in those studies which did monitor apoproteins (Niaura et al., 1991). Clearly, the findings across investigations are inconsistent. However, the studies vary greatly in terms of experimental design and measurement of other factors which may influence the level of lipids and lipoproteins independent of a purely psychological stress effect. In part to monitor such

8


effects, a few studies included a contiguous comparison group of unstressed subjects. Among this group of investigations, a mixed picture emerges, with some (Bijlani et al., 1983; 1986; O’Donnell et al., 1987; Trevisan et al., 1986) but not all (Netterstrom et al., 1988; Niaura et al., 1991) providing support for the hypothesis that behavioral stress has a significant impact on lipids. A few studies simultaneously measured or actually controlled other behavioral factors, such as dietary variables, physical activity and smoking, to test whether any effects of stress on lipids may simply be a result of changes in these variables. Results from these studies have been inconclusive, but one well-designed investigation indicated that controlling dietary factors resulted in no effects of stress on lipids. In this study, dietary influences were controlled by providing meals to subjects for the duration of the investigation (Flynn et al., 1984). This study in particular raises serious doubt about the importance of commonly occurring stressors, such as examinations or a temporary increase in occupational workload, in producing meaningful changes in serum lipids. It is possible that stressors which are in some ways larger in magnitude or which convey more personal threat may be more likely to produce significant changes in serum lipids. Two studies stand out as particularly salient on the dimension of personal meaning and threat. Gill et al. (1985) found that the levels of total cholesterol increased in response to a period of uncertainty corresponding to notification of selection for line command among American military officers. Notification was particularly meaningful because some assignments were to active combat areas. Trevisan et al. (1986) found that levels of total cholesterol and triglycerides were increased significantly in subjects who experienced a magnitude 6.8 (Richter scale) earthquake in Southern Italy in 1980. There were reports of 4441 deaths, 50,000 injuries and 280,000 left homeless. No changes in these parameters were noted in an age- and weight-matched group which was not exposed to the earthquake. Notably, the elevations in cholesterol and triglycerides were found 2 months after the disaster, suggesting that the response was not transient. Related to the issue of relevance is assessment of the subjective meaning and individual impact of the stressor. This is particularly important in situations where the level of threat or risk is not readily apparent. For example, students may be well prepared for anticipated examinations, and workers may already have had experience coping with expected and temporary increases in workload. Thus, prior experience, predictability of the stressor and its features, preparation and coping activities can all influence the response to a stressor, so it may be unreasonable to suppose that a stressor will have profound or similar effects among individuals unless that stressor clearly taxes the limits of coping capacity. In one study, an objectively defined increase in workload did not produce any change in lipids (McCann et al., 1990), but perception of increased stress and workload was significantly

R. Niaura et al. / L.ipids in psychological

research

9

related to an increase in the level of total cholesterol. However, in the only other study of episodic stress which assessed subjective effects of stressors, perceptions were unrelated to lipid changes (Niaura et al., 1991). Another way to gauge the impact of a stressor is to assess corresponding physiological indicators that are likely to be affected by the stressor. Unfortunately, the findings among the studies which assessed physiological responses concurrent with lipids are inconsistent. For example, although some studies observed increases in heart rate (Trevisan et al., 1986) and blood pressure response to the stressor consistent with lipid changes, others did not (OrthGomCr, 1983; Pincomb et al., 1987). In one study, although venous epinephrine and norepinephrine levels increased during stress, as did total and LDL cholesterol, the stress hormone response did not correlate with the lipid response (O’Donnell et al., 1987). The failure to correlate lipid changes with neuroendocrine adjustments does not necessarily negate the findings from this study; in fact, it may indicate that the time course of changes in these parameters during or after stress may differ, and thus gives us further information regarding the mechanisms by which stress may alter lipid metabolism. Because so few studies have simultaneously assessed subjective, physiological and lipid responses during stress, it is premature to conclude that episodic stressors are either able or unable to alter lipid levels. The inconsistencies in the existing literature raise the intriguing possibility that individual differences in the perceptions of stress may interact with the magnitude of stress to affect lipid changes. For example, subsets of individuals, e.g. those who report more subjective distress, may be identified who are likely to respond to stressors with an increase in circulating lipids. Clearly, more carefully executed studies of lipid responses to episodic stress are warranted. Chronic stressors Studies of the effects of chronic stressors have focused primarily on occupational stress, and most have reli.ed on cross-sectional designs to examine the strength of association between stress and lipids (Table 2). Assessments of job stress have usually been based on subjects’ reports of job performance requirements and the work environment (e.g. self-rated work demand, tension, instability). Several studies have also relied on an imputation strategy to assign ratings of job psychological demand and decision latitude based on job classification (e.g. Pieper, LaCroix & Karasek, 1989). Less common are case-control studies, in which subjects engaged in a stressful occupation (e.g. air traffic controller, prison guard), or who were exposed to stressful conditions (e.g. combat), were compared with their less stressed counterparts. Studies including a within-subject design component are uncommon.

et al. (1985)

Hendrix

et al. (1990)

et al. (1986)

Mattiasson

Howard

Hollis et al. (1990)

et al. (1981)

stressors

Chesnev

Table 2 Studies of chronic

Within


Self-reported job role ambiguity

Economic instability, threat of unemployment, distursleep bance

Managerial and professional men (N = 217)

Male shipyard workers (n = 715) and male agematched controls (n = 261)

subjects

Cross-sectional

Cross-sectional

Hospital and Department of Defense employees (N = 370) Men at risk for cardiovascular illness participating in the MRFIT (N = 12866)

Cross-sectional

Perceived social climate of work unit (Work Environment Scale) Job stress and life stress composite ratings Total number of life events and loss events

Managers at missile and space company (N = 384)

No association between any of 10 Work Environment Scales and total, HDL and LDL cholesterol. Measures of stress unrelated to HDL/total cholesterol ratio. Significant but small (rs = - 0.05 and - 0.03) negative associations between events and total cholesterol. Increase in job role ambiguity related to increse in triglycerides, but not cholesterol, in Type A men. Effect strongest for Type As who were least hardy (more dependent). Shipyard workers showed an increase in total cholesterol, but not triglycerides, after they experienced economic instability, relative to controls. Workers directly threatened with unemployment showed an increase in cholesterol, but not triglycerides, compared with those who were not. Within the workers, change in sleep disturbance was positively correlated with cholesterol change.

?J

6

et al. (1991)

Pieper

et al. (1989)

Orth-Comer and UndCn (1990)

Ohara

Maxwell et al. (1983)

Job psychological demands and decision latitude Job psychological demands and decision latitude

Primarily white collar workers in aerospace industry: WCGS (N = 3023) Federal employees in health, postal, aerospace and other agencies: EHS (N= 2379)

Cross-sectional

Cross-sectional

Cross-sectional

Job psychological demands and decision latitude

of (N

sample NHES

Representative US occupations: = 2291)

Cross-sectional

Cross-sectional

Cross-sectional

Between jects, case trol

Cross-sectional

sample of NHANES

Representative US occupations: II (A’= 2925)

characteris-

Self-rated job, home and financial stress Work demand (tension/pressure and overtime ratings) Job physiological demands and decision latitude

Job tics

Job psychological demands and decision latitude

sample of NHANES

Representative US occupations: I (N= 1937)

Japanese (n = 670) and American (n = 829) telephone executives Swedish male workers (N = 1501

Air traffic control officers (n= 67) and age, smoking and measurement time matched community controls (n = 1005) subcon-

of

stress

on

Negative relationship between decision latitude and total cholesterol. No effect for psychological demands. Negative relationship between decision latitude and total cholesterol. No effect for psychological demands,

Decision latitude positively related to total cholesterol. No effect for psychological demands. Decision latitude positively related to total cholesterol. No effect for psychological demands. No effect of decision latitude or psychological demands on total cholesterol.

No association between work demand and total cholesterol or triglycerides.

No effects HDL.

No differences in total or HDL cholesterol between air traffic control officers and matched controls.

males (n = 75) ex-

Sorensen

et al. (1985)

Siegrist et al. (1988)

Employed community ple (N = 2500)

sam-

Cases with coronary artery disease (n = 72); age- and sex-matched visitor controls (n = 72); and patients without disease (n = 40) German blue collar workers (N = 254)

Sibai et al. (1989)

males (n = 35)

Men of Japanese ancestry living in Hawaii (N = 8006)

nonexposed

posed to noise and healthy,

Healthy

Reed et al. (1989)

Rai et al. (1981)

Table 2 (continued)

Presence or absence of high occupational instability, high perceived job insecurity, high work demand, high perceived workload Work hours, deadlines, occupational mobility. Reported stress symptoms.

Job psychologi cal demands, and decision latitude War-related stress

Exposure to daily workplace noise (88-107 dB(A)) for lo-15 years

Cross-sectional

Between jects/within jects

Between jects, case trol

subsub-

subcon-

subjects

Cross-sectional

Between

Occupational instability by job insecurity interaction for LDL/HDL ratio, LDL, HDL and apo B; not for apoA1. Work demand by perceived workload interaction for LDL/HDL ratio, HDL, apoA1; not for LDL or apoB. No associations with total cholesterol.

Free cholesterol and ratio of free to esterified cholesterol higher in the exposed group. No difference in total or esterified cholesterol. No effect of decision latitude or psychological demands on total cholesterol. Hyperlipidemia more prevalent in cases vs. visitor controls.

et al. (1983)

Webster Prison officers (n = 262), blood doners (n = 600), random population sample (n = 2770)

men (N =

Coronary-prone 416)

et al. (1983)

Trevisan

Male myocardial infarction survivors (N = 116)

Secluded nuns (n = 144) and laywomen (n = 138)

et al. (1987)

Timio et al. (1988)

Theorell

Occupational stress

Self-rated sion

ten-

Subjective ratings of job psychological demands, work variety, influence over work, intellectual discretion at work, and demands divided by variety, influence, and intellectual discretion, respectively. Societal isolation vs. exposure

Between

subsub-

subjects

Crosssectional/within subjects

Between jects/within jects

Cross-sectional

Significant increase in total cholesterol for tension vs. no tension. Difference noted in tension --) no tension, but not no tension + tension within subjects analysis. Prison officers more likely to have elevated triglycerides but not total cholesterol compared with control groups.

Significant but similar increase in total cholesterol and triglycerides in both groups over time (20 years).

Total cholesterol correlated positively only with demands divided by influence. Triglycerides and LDL/HDL ratio uncorrelated with any rating.

14


research

With few exceptions, the studies of chronic occupational stressors fail to show significant associations between stress and lipids. Although statistical inference is weakest with cross-sectional data, and control over other factors which may affect lipids varies considerably among the studies, the consistency of the negative findings and the rather large sample sizes of some of the studies suggests that the relationship between job-related stress and lipids is nonsignificant. Moreover, several of the studies which measured such factors as age, sex, relative weight, diet, exercise, cigarette smoking, and controlled for these effects statistically, failed to show the expected interaction between stress and lipids (McCann et al., 1990; Reed, LaCroix, Karasek, Miller & Maclean, 1989). However, no published study examining the impact of chronic stress on lipids and lipoproteins has measured or controlled several of these key parameters simultaneously. The five studies reported by Pieper et al. (1989) are of particular interest. All of the studies used a common imputation strategy to assess job psychological demands and decision latitude, and the studies applied these methods to five large data bases, three of which included representative samples of US workers (i.e. NHANES I and II and NHES). The imputation strategy assigns to individuals a score for job psychological demands and decision latitude based on their occupation. The scores were derived from prior survey research in which these indicators were standardized within occupations, controlling for the effects of other sociodemographic features. Thus, individuals within a certain occupation were assigned a score which is the average standardized score for that occupation. This enables assignment of psychologic demand and decision latitude scores when only occupation is known. In addition to main effects, the authors were interested in the interaction between demands and latitude. Thus, they expected that high job strain, defined as high job demands combined with low decision latitude, would be associated with increased cardiovascular risk. Of the five studies, two showed an effect for decision latitude on total serum cholesterol in the predicted direction, two in the opposite direction, and one showed no association. No effects were found for psychological demands in any of the studies. When the results were combined in a meta-analysis representing 12,555 individuals, no main effects were found, and there was no interaction between demands and latitude on the level of total cholesterol, thus refuting the strain hypothesis. Another large study, using similar methods, replicated these negative findings (Reed et al., 1989). Pieper et al. (1989) correctly note that the imputation strategy for assigning job demand and decision latitude scores suffers because individual variation in these components is not assessed. Thus, one might expect to find stronger relationships between stress effects and lipids in studies which directly assessed subjects’ perceptions of demands and latitude. As noted previously, though, most studies that assessed perceptions of job-related


research

15

stress failed to find the expected

association with lipids (e.g. Chesney et al., 1981; Hendrix, Ovalle & Troxler, 1985; Orth-GomCr & UndCn, 1990). However, in one study, perceived job insecurity and an objective indicator of occupational instability, a 20% workplace reduction in personnel, interacted to detrimentally affect levels of LDL, apoB, HDL and the LDL/HDL ratio (Siegriest, Matschinger, Cremer & Seidel, 1988). Thus, controlling for age, body weight and smoking, men who worked in an environment in which the workforce was reduced by 20%, and who simultaneously perceived their own job security to be low, showed the worst lipid profiles. It is noteworthy that these findings remained stable over a 2 year period. The study by Siegrest et al. (1988) points again to the importance of considering the interaction between a stressful event and the subjective reaction to that event in relation to cardiovascular risk. These data could also be interpreted as supporting the hypothesis that severity of the stressor is an important consideration in producing an effect on lipids. Thus, while variations in job demands and decision latitude are sure to influence subjective levels of distress, the real and perceived threat of unemployment may be more salient than variations in other dimensions of job stress. The study reported by Mattiasson, Lindgarde, Nilsson & Theorell (1990) also supports the contention that severity of the stressor is an important consideration. They found that male shipyard workers who were directly threatened with unemployment showed a significant increase in total cholesterol concentration relative to men who were not directly threatened. In this study, the period of uncertainty preceding actual layoffs occurred for a year prior to the follow-up testing, and testing continued for almost a year after some of the men received direct notice of impending layoffs. Thus, the stressor could be considered severe, in that a person’s livelihood was directly at stake, and it could be considered chronic, in that the process of notification extended over a period of years. The positive results are consistent with findings reported earlier (Kasl, Cobb & Brooks, 1968). In another study reporting positive findings, hyperlipidemia was found to be more prevalent in coronary angiography patients who had significant and life-threatening combat experiences relative to angiographic patients who had not had such experiences (Sibai, Armenian & Alam, 1989). Finally, one study deserves mention because of the impressive follow-up and unique nature of the stressor. Timio et al. (1988) reported a 20 year study of nuns who were largely secluded from society compared with a group of laywomen. Although higher at study entry in the nuns, serum triglycerides and total cholesterol increased similarly in both groups over time. However, systolic blood pressure levels increased significantly more for the laywomen. Age, race, ethnic background, age at menarche, family history, diet and contraceptive use were assessed and did not affect the results. The authors concluded that the differences in blood pressure reflected the effects of the


16 Table 3 Experimental Authors

and correlational

(yr)

studies

of response

Subjects

to acute stressors

Stressor

Results

Experimental studies Arnetz

et al. (1985)

Male psoriasis patients (n = 10) and healthy male medical students (n = 10)

Color-word conflict task (40 min); Mental arithmetic (10 min)

Arnetz (1986)

and

Male medical students and employees(N=20)

Color-word conflict test (40 min); Mental arithmetic (IO min) Public speaking (30 min)

Fjellner

Balm-Audorff (1989)

Comens

et al.

et al. (1987)

Davis and Matthews (1990)

Henrotte (1985)

et al.

Healthy IO)

males (N =

Male fighter pilots and weapon system officers (N = 11) Female smokers (N = 35)

Surface attack training missions (45 mins) Social-evaluative speech task (4 min preparation and 4 min delivery)

Type A (n = 20) and Type B (n = 19) students

Signal detection task with backgroundnoise

No change in total cholesterol or triglycerides during either task. No differences between groups. Increase in triglycerides across both tasks. Total and HDL cholesterol increased significantly shortly before and after the speech relative to a control day. LDL, LDL/ HDL ratio, and triglycerides did not change. Epinephrine and norepinephrine levels correlated positively with total cholesterol level after the speech. No change in HDL cholesterol. Increases in total, LDL, HDL cholesterol, triglycerides and FFA. Increases in total, LDL and FFA larg est for subjects who smoked prior to task. Increases in triglyceride and total cholesterol largest for oral contraceptive users. Increases in FFA in both groups, although increase larger in Type A students.

17

R A&urn et al. / Lipids in psychological research Table 3 (continued) Authors

(yr)

Stressor

Subiects

Results

Experimental studies Joborn

et al. (1990)

Healthy

Kemmer

et al. (1986)

Larssen

et al. (1989)

Healthy

et al. (1985)

91 Healthy male cal students

Lovallo

Matthews (19911

et

al.

Color-word conflict task (25 min) Mental arithmetic Public (45 min); speech (10 min); Preparation 5 min speech; Snoop task (25 min)

males (N =

9) Healthy (n = 9) and Type 1 diabetic (n = 18) volunteers

males (N =

29) Healthy men 26) and women

Active vs. passive avoidance of aversive noise (15 min) Mirror tracing (10 min); Stroop task (10 min)

medi(N= (n = (n =

26)

Schwaberger Sedgwick (19811

Spence

(1987)

et al.

Male racing car drivers (N = 20) Healthy men (N = 12)

et al. (1990)

Untreated border line hypertensives (N=40)

-

Car races (several hours) Sexually explicit film (13 mitt); Speech (5 min); Puzzle task with electric shock (30 min) Mental arithmetic min); Mirror (12 tracing (12 min)

Free fatty acids increased. No change in FFA during either task.

Free fatty acids increased. Increase in FFA with both tasks. Increases in total, LDL and HDL cholesterol during mirror tracing; no changes in triglycerides or FFA. Increases in total, LDL, HDL cholesterol, FFA and triglycerides during Stroop test. Men showed greater changes in LDL than women during the Stroop test. Increase in FFA. No change cholesterol glycerides tasks.

in total and triacross

Increases in total, HDL cholesterol; no changes in VLDL, LDL, triglycerides or apo B during arithmetic. Increases in VLDL, LDL, HDL cholesterol, no changes in total cholesterol, tri glycerides and apo B during mirror tracing.

18


research

Table 3 (continued) Authors

(yr)

Subjects

Stressor

Results

Experimental studies Stoney

et al. (1988)

Healthy men 22) and women 19)

Stoney

et al. (1990)

Healthy = 15)

Takeshima (1989)

Villani (1991)

et

and

al.

Singer

women

(n = (n =

Mental arithmetic (2 min); Social evaluation speech task (2 min preparation, 3 min speech); Speech self-evaluation task (3 min)

(N

Social evaluative speech task (2 min preparation, 3 min speech); Mental arithmetic (6 min); Isometric exercise (2.5 min) Cold pressor test (1 min)

Headache patients (n = 28) and healthy, age-matched controls (n = 14) Healthy volunteers (N=13)

Videogame

(15 min)

Correlational Fredrikson and Blumenthal (1988)

Male MI patients (N = 42) divided into high risk (n = 21) and low risk (n = 21) groups based to 0 n tal cholesterol/ HDL ratio

Increases overall in LDL during all tasks, HDL and triglycerides during speech and selfevaluation, and FFA during self-evaluation. Males showed largest LDL increase during all tasks. Males showed increase in apo AI during speech; no change in apo AI1 or apo B for males or females during speech. Increase in LDL cholesterol during arithmetic and exercise. No change in HDL or HDL,.

No change in FFA. No effects of group.

Increase in FFA. Increase attenuated by ingesting glucose.

Studies

Mental arithmetic (15 min)

No difference between high and low risk groups in heart rate and blood pressure during arithmetic, but norepinephrine change greater in high risk group. In a separate analysis, high catecholamine reactors (median split) had higher total cholesterol and total cholesterol/HDL ratio than low reactors.


19

research


(yr)

Subjects

Stressor

Healthy male students (N = 106)

Cold pressor

Experimental Gillum

et al. (1981)

Results studies (1 min)

Jorgensen (1988)

et

al.

Unmedicated hypertensive tN=59)

mild males

Videogame (5 mink Stroop task (2 min)

Lundberg (1989)

et

al.

Male (n = 30) and female (n = 30) white collar workers

Star tracing, mental arithmetic, colorword conflict, cold pressor, hand grip, Type A interview (60 min)

Physicians (n = 48), dentists (n = 2); (only 1 female)

Videogame (5 mink Mental arithmetic (3 mink Cold pressor

McKinney (1987)

et

al

(90 s)

Absolute levels of SBP and change from baseline correlated positively with total cholesterol. High heart rate reactors (median split on averaged change scores) had higher levels of total cholesterol and triglycerides than low heart rate reactors. Norepinephrine response across all stressors correlated positively with total and LDL cholesterol and triglycerides in women. Epinephrine and norepinephrine response correlated negatively with triglycerides in men. Increases in DBP during cold pressor correlated positively with total cholesterol. Increases in DBP and MAP during mental arithmetic correlated positively with triglycerides. HDL associated negatively with DBP and total systemic resistance during arithmetic, and negatively with total systemic resistance during the cold pressor.

20


research


(yr)

Subjects

Stressor

Type A (n = 13) and Type B (n = 11) healthy males

Mental

Results

Experimental Suarez

et al. (1991)

studies

arithmetic

Total cholesterol negatively correlated with DBP increase overall. Epinephrine change positively correlated with total and LDL cholesterol overall. Type A, but not Type B, subjects showed positive correlations between epinephrine, norepi nephrine, cortisol changes and total and LDL cholesterol.

low stress environment for the nuns compared with the higher stress experienced by the laywomen. If we assume that the laywomen experienced more stress over 20 years than did the nuns, then the results suggest further that serum lipids are not likely to be affected by the stresses and strains of everyday life. Thus, there is little evidence that occupational stress per se acts to influence levels of lipids and lipoproteins detrimentally. However, when job stress consists of economic instability and actual threat of unemployment, significant effects are more likely to occur. Therefore, the effects of chronic occupational stress may only be uniformly evident when the stressor involves a threat to one’s wellbeing. Moreover, it is possible that objective and subjective indicators of stress interact to have some effect on lipids. Stated differently, perhaps individuals must both experience some real threat and perceive this threat to be important before alterations in lipids are apparent during chronic situations. Acute laboratory

stressors

Studies of acute laboratory stressors are generally experimental studies which examine lipid/lipoprotein responses to acute challenges (Table 3). Generally, the laboratory stress studies have relied upon tasks such as mental


research

21

arithmetic, video game, speech and color-word conflict tasks to evoke physiological responses. Task duration varied considerably among the studies, but the stressors were rarely presented for more than a few minutes at a time. The results of the experimental studies are reasonably consistent in showing an increase in FFA in response to acute stress. For example, of eleven studies which looked at FFA, nine noted an increase. These results are also consistent with prior research (Dimsdale & Herd, 19821, and consistent with what is known about sympathetic nervous system physiology and lipid mobilization. For example, enhanced sympathetic nervous activity as a result of stress may lead to a concomitant release of catecholamines. It is known that catecholamines can directly stimulate adipose tissue, resulting in lipolysis and release of FFA into the circulation (Hjemdahl & Linde, 1985). The rapidity of such a system has great survival value in preparing the organism for muscular activity by providing a quick energy substrate. Several of the experimental studies also examined responses of other lipids and lipoproteins to acute stress and noted increases in total, LDL and HDL cholesterol (Davis & Matthews, 1990; Matthews, Davis, Stoney, Owens & Caggiula, 1991; Spence et al., 1990; Stoney, Matthews, McDonald & Johnson, 1988; Stoney, Owens, Mathews, Davis & Caggiula, 19901, and an increase in triglycerides (Arnetz & Fjellner, 1986; Davis & Matthews, 1990; Matthews et al., 1991; Sedgwick et al., 1981; Spence et al., 1990; Stoney et al., 1988). However, even within and between the positive studies, the results are not entirely consistent, and responses vary with the type of stressor used and the subjects who are studied. For example, one study found that subjects responded to mental arithmetic with increases in total and HDL cholesterol, but no change in the levels of very low density lipoprotein (VLDL) or LDL cholesterol, triglycerides or apolipoprotein B (Spence et al., 1990). In contrast, during a mirror tracing task, the same subjects showed an increase in VLDL, LDL, and HDL cholesterol, but no change in total cholesterol, triglycerides or apolipoprotein B. It is presently unclear whether these discrepancies are due to low statistical power and measurement error; to true differences which may be related to the task characteristics and the distinctive pattern of physiological response which each task evokes; or to other individual differences. Some of the studies have found that males are more likely than females to show increased LDL cholesterol response to acute stress (Stoney et al., 19881, and that smoking and oral contraceptive use potentiate the lipid response to acute stress (Matthews et al., 1991). These findings are of interest because they parallel epidemiological evidence which has implicated male sex, smoking and oral contraceptive use as factors associated with an atherogenic lipoprotein profile. The studies reviewed here further suggest that these factors may interact with the response to stress to elevate circulating levels of atherogenic lipids.

22


Conclusions Our overall conclusions regarding the literature examining the effects of stress on alterations in lipids are mixed. While there is sporadic evidence that naturalistic stressors, whether episodic or chronic in nature, are sometimes associated with changes in lipid parameters, more studies have failed to find such associations. It is likely that the severity and consequences of the stressor interact with individual perceptions regarding that stressor to impact on lipid metabolism. Support for this notion comes from the fact that most investigations of severe stress or of individuals who perceive themselves as greatly threatened demonstrate an alteration in lipid levels in the direction of a more atherogenic profile. In contrast to studies of chronic stress, experimental studies of acute laboratory stress provide good evidence for behavioral stress eliciting shortterm increases in FFA. Several of these investigations have also shown an increase in total cholesterol and some lipoproteins in response to acute stress. Investigations such as these may be particularly effective in shedding light on the psychophysiological mechanisms which link the experience of stress with development of an atherogenic lipoprotein profile. Several factors make definitive conclusions regarding this literature problematic. Researchers still rely primarily on within-subject designs which cannot control for nonspecific and secular effects. Despite the fact that a few recent studies have included contiguous comparison groups, even these methodologically superior studies provide inconsistent results. Increasing attention has been paid to assessment of other factors which are known to affect blood lipids, e.g. diet, activity and smoking, but these factors have not been shown to affect the stress-lipid relationship in studies with either positive or negative results. Many investigations have generally focused on a narrow range of stressors and populations, in particular academic examinations and students, so it is not yet clear whether other kinds of commonly occurring episodic stressors (e.g. anger- and anxiety-provoking situations) can influence serum lipids and lipoproteins. Related to this issue, sample sizes have been generally small. Small sample sizes of limited populations and stressors bring into question the generalizability of these studies to other sample characteristics and stressors, as well as the issue of whether power to enable detection of true effects may have been lacking in some studies. Finally, we believe that, until we understand the mechanism(s) by which stress may impact on lipid metabolism, discrepancies in the literature are inevitable. In the final section of this paper, we outline several potential pathways by which psychological and behavioral factors may impinge on lipid metabolism. We feel it is essential that future studies be directed to delineating these and other putative pathways, in order to comprehend the stress-disease relationship.

R Niaura et al. / Lipids in psychological

Individual

research

23

differences

In this section, we consider individual differences which influence lipid and lipoprotein levels. Published studies included in this section were identified in a way similar to the manner in which the studies of stress and lipids were identified. However, instead of including only studies published in the previous 10 years, we opted to include investigations published since 1956 because the earlier studies were not represented in the Dimsdale and Herd (1982) review. The majority of these studies that we identified only examined the effects of individual differences in psychological dimensions which bear some relationship to resting levels of lipids and lipoproteins, and not how these psychological dimensions may modulate lipid responses to stress. In this section, we also present the few studies which have examined the interaction of other, biological individual differences and lipid responses to psychological stress. Included in the former group are studies pertaining to the Type A behavior pattern and its subcomponents; personality, coping style, and mood; and social support. Included in the latter group are studies investigating the effects that gender and an elevated risk for CHD have on modifying the lipid response to behavioral stress. Type A behavior and subcomponents

Several studies have examined the association between the global Type A behavior pattern (TABP), defined and measured in various ways, and blood lipids. Friedman, Rosenman and colleagues were the first to report on such associations, and they noted that both men (Friedman & Rosenman, 1959; Friedman, Byers, Rosenman & Elevitch, 1970; Friedman, Rosenman & Byers, 1964; Rosenman & Friedman, 1963) and women (Rosenman & Friedman, 1961) who displayed TABP were more likely to have higher levels of total cholesterol than their Type B counterparts. One study found that Type A men also showed elevations in levels of serum triglycerides, LDL and VLDL cholesterol, and decreases in HDL cholesterol, relative to Type B men (Rosenman & Friedman, 1963). In all of the studies, the relationship between behavior pattern and serum lipids could not be ascribed to differences in age, diet, weight, smoking or physical activity. However, Type A subjects were more likely than Type B subjects to show increased blood clotting times and daytime urinary excretion of norepinephrine (Friedman, St. George, Byers & Rosenman, 1960). In two studies, subjects were provided with a high fat meal after fasting, and serum triglycerides were monitored for a period of some hours afterward (Friedman & coworkers, 1964, 1970). In both studies, Type A men showed a greater increase in triglyceride concentration in response to the fat challenge (i.e. poorer clearance) than did Type Bs. This suggests that a difference between Type As and Bs in the ability to

24


research

metabolize triglycerides might account for differences in lipids assessed during a fasting state. Since Friedman, Rosenman and colleagues published their reports, several additional studies have examined the strength of association between behavior pattern and serum lipids. About half of the additional studies we could find provided qualified support for an association (Cohen & Reed, 1985; Howard, Cunningham & Rechnitzer, 1976; Hubert, Eaker, Garrison & Castelli, 1987; Lovallo & Pishkin, 1980; Lundberg, Hedman, Melin & Frankenhaeuser, 1989; Orth-GomCr & UndCn, 1990; Shekelle, Schoenberger & Stamler, 1976; Sprafka, Folsom, Burke, Hahn & Pirie, 1990; van Doornen, 1980; Watkins, Fisher, Southard, Ward & Schechtman, 1989). We qualify the conclusions because positive associations were often, and inconsistently, influenced by sex, age, race, and the type of lipid measured. Several studies have also failed to find any evidence for an association between behavior type and serum lipids (Chesney et al., 1981; Eaker, Abbot & Kannel, 1989; Friedman, Hellerstein, Eastwood & Jones, 1968; Gallacher, Yarnell & Butland, 1988; Garrity, Kotchen, McKean, Gurley & McFadden, 1990; Hendrix et al., 1985; Keith, Lown & Stare, 1965; Kornitzer, Drama& DeBacker & Thilly, 1977; Simon, Kruiej, &arc & K%ek, 1983; Sorensen et al., 1985; van Doornen & van Blokland, 1989). In the Western Collaborative Group Study (N = 3154), although the correlation coefficient between behavior pattern type and total cholesterol in participants at the study baseline was statistically significant (r = .057), the magnitude of the relationship was quite small (Brand, 1978). It is unclear whether differences in study populations or methods, including definition and assessment of TABP, can account for the discrepant findings. A great deal of attention has been focused on hostility as a subcomponent of TABP, because anger and hostility are thought to be particularly pathogenic for CHD (Diamond, 1982). Some studies have found that aspects of hostility and aggression bear a positive association with serum lipids. In a group of 26 normal students, Sloane, Habib, Eveson & Payne (1961) found that individuals with an elevated level of total cholesterol rated themselves as higher on hostile attitudes and total hostility than those with normal cholesterol levels. Jenkins, Rosenman & Friedman (1966) found that, in a group of 100 men, high ratings of hostility obtained during the Structured Interview assessment for TABP were related to increased levels of LDL cholesterol and an increased LDL/HDL ratio. In this study, high drive (striving for achievement) and high motor signs indicative of TABP were also related to elevations in total cholesterol. Harlan, Oberman, Mitchell & Graybiel (1967) found that, in a group of 441 men, the aggressiveness subscale (lack of restraint) on the Guilford - Zimmerman Temperament Survey (Guilford & Zimmerman, 1949) correlated positively with very low density lipoproteins, total cholesterol and triglycerides. Moreover, this association was indepen-

R. Niaura et al. / L.ipidsin psychologicalresearch

25

dent of the influence of weight, diet, family history of heart disease, smoking and physical activity. Recently, using a Swedish version of the Videotaped Structured Interview, Lundberg, Hedman et al. (1989) found that ratings of hostile/aggressive behavior were positively related to levels of total cholesterol in both men and women. Recent studies which have relied on MMPIderived measures of hostility, such as the Cook-Medley Hostility Scale (Cook & Medley, 19541, however, have failed to show a positive relationship between total cholesterol and hostility (Almada et al., 1991; Niaura et al., 1991; Scherwitz et al., 1991; Shekelle, Gale, Ostfeld & Paul, 1983). Because hostility itself is a construct comprising multiple cognitive, attitudinal and behavioral aspects, it is possible that, like TABP, only some of the underlying dimensions are related to serum lipids. Three studies also found that TABP interacted with some personality dimension to elevate lipids. Thus, Type As who were also hostile (Weidner, Sexton, McLellarn, Connor & Matarazzo, 1987), or less hardy (Howard, Cunningham & Rechnitzer, 19861, or more field-dependent (McCranie, Simpson & Stevens, 1981) were more likely to show elevations in lipids then were Type As who did not possess these additional attributes. Thus, consideration of TABP subcomponents and interactions among components may help to explain some of the discrepancies in results of studies reviewed above. Personality,

coping style and mood

As noted above, there is some evidence to suggest that hostility and aggression may be related to elevations in serum lipids. To the extent that these attributes can be thought of as relatively enduring traits, we may conclude that certain aspects of personality are related to serum lipids. We review briefly here the results of some other studies that investigated other aspects of personality, coping style and depressed mood. In two studies, Jenkins, Hames, Zyzanski, Rosenman & Friedman (1969) found that scores on the Socialization and Self-acceptance subscales of the California Psychological Inventory correlated positively with levels of total cholesterol. The results were not influenced by age, occupation, education or cigarette smoking. High scores on the Socialization subscale are thought to reflect the tendency to adhere to social norms, and to be dependable, conscientious and proper. High scores on the Self-acceptance subscale are thought to reflect the characteristics of passivity, self-criticism and proneness to feelings of guilt. Jenkins et al. (1969) also reported that in one of the studies, LDL cholesterol was elevated in men who repressed their anxiety, as measured by the Welsh Anxiety and Repression scales. The authors interpreted the sum of the findings to suggest that excessive “over control” was related to lipid elevations. Consistent with this interpretation, Thomas, Ross

26


& Duszynski (1975) reported that elevated total cholesterol was associated with less self-rated depression, anxiety, nervous tension, and demonstrativity within the family. Several recent unpublished reports have also suggested that repression of anxiety (King, Albright, Barr Taylor, Haskell & DeBusk, 1986; Niaura, Herbert, McMahon & Sommerville, in press) and suppression of aggression (Weinberger, 1991) are related to higher levels of total and LDL cholesterol. In two of the studies, the results were found to be independent of age, smoking and body mass index effects (Niaura et al., in press; Weinberger, 1991). A growing body of literature indicates that individuals who characteristically repress anxiety (assessed usually by the combination of MarloweCrowne and Taylor Anxiety Scales) evidence greater cardiovascular responsiveness to acute stressors than do nonrepressors (Asendorpf & Scherer, 1983; King, Albright, Taylor, Haskell & DeBusk, 1990; Warrenberg et al., 1989). Moreover, repressive coping has been associated with higher resting blood pressure (King et al., 1990; Warrenberg et al., 1989). It is conceivable, therefore, that the mechanisms responsible for augmenting resting and stress-related cardiovascular parameters in repressors (e.g. enhanced SNS drive) may also be responsible for elevating levels of total and LDL cholesterol. A few studies have noted that field-dependence is related to lipid levels. Field-dependent individuals tend to be influenced more by external frames of reference in processing information, and they are more likely to show signs of heightened tonic autonomic arousal than are field-independent individuals. Flemenbaum and colleagues (Flemenbaum & Flemenbaum, 1975; Flemenbaum & Anderson, 1978) reported that field dependence is associated with elevations in total cholesterol, and others have reported that field-dependent individuals have elevations in FFA levels at rest and in response to saline or insulin injections (McGough, Silverman & Bogdonoff, 1965). Moreover, one study has reported that field dependence and the Type A behavior pattern interact to elevate total and LDL cholesterol (McCranie et al., 1981). This latter study illustrates the importance of identifying the particular aspects of personality characteristics that are salient with regard to modifying lipid levels. In contrast to the null findings of some previously reported studies (e.g. Thomas et al., 1975), there are some reports of positive associations between depression, anxiety and lipids. For example, among men undergoing job loss, nurses’ ratings of depression, anxiety, sadness and low self-esteem were related to higher levels of total cholesterol (Kasl, Cobb & Brooks, 1968). However, this was true only among the subset of men who were judged to be flexible and nondefensive. Segers & Mertens (1976) found that self-reported anxiety and depression were positively correlated with levels of total cholesterol and triglycerides, but only in obese subjects under the age of 45. van


research

27

Doornen (1980) found that self-rated depression correlated with resting levels of total cholesterol, but in subsequent studies he found that this relationship was either restricted to males (van Doomen & van Blokland, 1987) or nonsignificant (van Doomen & van Blokland, 1989). However, in the latter two studies, personality variables were found to interact with a stressor to influence change in total cholesterol during stress. In one study, the increase in total cholesterol due to an examination stressor correlated positively with ratings of depression and achievement motivation (van Doornen & van Blokland, 1987). In the other study, ratings of vital exhaustion, characterized by excess fatigue, decrease in energy, and dejection, correlated positively with increases in total cholesterol during academic examinations (van Doornen & van Blokland, 1989). These studies are noteworthy in that they are the only ones we are aware of which provide evidence for an interaction between some predisposing individual characteristic and the lipid response to a naturally occurring episodic stressor. Social support To our knowledge, very little work has been done to explore the direct or indirect effects of social support on serum lipids. In one study of healthy, elderly adults, high levels of perceived social support were associated with lower serum cholesterol and uric acid levels and higher indices of immune function (Thomas, Goodwin & Goodwin, 1985). The results were independent of the effects of age, body mass index, smoking, alcohol intake and degree of perceived psychological distress. In another study, effects of job loss on levels of total cholesterol in a sample of male factory workers was studied over a period of 2 years (Gore, 1978). Men were divided into three groups: (a) those who were promptly re-employed, (b) those who remained unemployed but who had high levels of social support and (c) those who remained unemployed with low levels of support. While anticipating unemployment, all groups showed similar levels of total cholesterol. When terminations occurred, only the unsupported men showed an increase in level of total cholesterol. At 1 and 2 years after job loss, the unsupported men still showed elevations in total cholesterol compared with the other two groups, even though 90% of them had found new jobs. While not definitive, these studies suggest that social support may have some direct and indirect, i.e. stress-buffering, effects on stress-induced increases in total cholesterol. Sex differences In all Western countries, males die of CHD at about twice the rate of females, after adjustment for age and all known risk factors (Wingard, Suarez, Barrett-Connor, 1983; Wingard, 1982). Studies examining sex differ-

28


ences in lipids and lipoproteins at rest have generally reported that males have higher levels of total and LDL cholesterol relative to females, and females have higher levels of HDL cholesterol and the ratio of HDL/LDL cholesterol relative to males (Hazzard, 1985). These sex differences are generally thought to be attributable to differences in reproductive hormones, and several studies have systematically investigated the effects of endogenous and exogenous sex hormones on lipids and lipoproteins. Although small fluctuations in circulating estrogens, such as might occur during the menstrual cycle, do not appear to dramatically influence resting or stress-associated lipid levels (Stoney, Owens, Matthews, Davis & Caggiula, 19901, larger differences in circulating estrogens and androgens, such as might occur between men and women, and among women given exogenous estrogens, probably do affect lipid levels. For example, postmenopausal estrogen replacement therapy given orally in low doses decreases LDL cholesterol and increases HDL cholesterol, the former effect being a result of increased LDL catabolism (Walsh, Schiff, Rosner, Greenberg, Ravnikar & Sacks, 1991). The lipid effects of premenopausal oral contraceptive use are dependent upon the relative concentrations, balance, and specific types of exogenous estrogen and progestin; in general, elevated LDL cholesterol and diminished HDL cholesterol are found in women using preparations with higher progestin concentrations than in women using lower progestin concentration formulas (Wahl et al., 1983). The existence of sex differences in reproductive hormones is one hypothesized explanation for the sex difference in CHD. To the extent that psychophysiological responses to stress are relevant to the development of CHD, the examination of sex differences in lipid and lipoprotein responses to stress is relevant. Investigations of sex differences in lipid responses to stressful situations are few. Some studies have tested sex differences in response to examination and chronic stressors, and these have most frequently found no significant sex differences in lipid responses. For example, one study found that total cholesterol was elevated during an examination stress about equally in males and females (van Doornen & van Blokland, 1987). Inspection of the data, however, suggests a trend for males to have greater changes during stress than females, since the mean increase in total cholesterol for males in this study was more than double that of females. It is important to note that the average response of males (7% increase) was biologically meaningful, as well as statistically significant. The few investigations of sex differences in lipid response to laboratory stressors have generally suggested that males and females respond differently. One systematic study found that young adult men have greater LDL cholesterol and total cholesterol changes during stress than do young adult women (Stoney, Matthews, McDonald & Johnson, 1988). Again, the magnitude of the effect for men, and particularly a subset of men, was robust. In a


29

follow-up study, it was again found that those who responded with the largest changes in LDL cholesterol during stress were more likely to be men, while those who responded with little or no change in LDL cholesterol during stress were most likely to be women (Matthews, Davis, Stoney, Owens & Caggiula, 1991). Finally, in a study of Swedish men and women, total cholesterol was significantly and positively correlated with systolic blood pressure during occupational and laboratory stress in men, but not women (Lundberg, Fredrikson, Wallin, Melin & Frankenhauser, 1989). These latter studies provide preliminary evidence that gender may be a particularly important variable in predicting lipid response to a variety of challenges, in addition to predicting resting lipid levels. High risk individuals Results from a few studies have suggested that the association between stress reactivity and resting lipid levels is subject to the influence of individual differences, particularly in high-risk individuals. For example, several correlational studies have examined the association between cardiovascular and neuroendocrine responses to stress and resting levels of lipids. Each investigation presents some evidence that sympathetic or adrenergic reactivity to the laboratory tasks. correlates positively with some index of atherogenie risk (e.g. levels of total cholesterol or total/HDL cholesterol ratio). This finding is potentially meaningful, because it could be interpreted as supporting the notion that increased stress-responsiveness is somehow related to an atherogenic lipoprotein profile, despite the fact that the direction of causation is unknown. It is particularly important to note that the effect is apparent only in studies of individuals at elevated risk for CHD or those with established disease (Fredricksen & Blumenthal, 1988; Jorgensen, Nash, Lasser, Hymowitz & Langer, 1988; Suarez, Williams, Kuhn, Zimmerman & Schanberg, 1991). For example, in a recent study, Suarez and colleagues (1991) found that Type A or high hostile males were likely to show a positive relationship between resting total cholesterol and the catecholamine and cortisol response to a mental arithmetic test, whereas for Type B and low hostile men the opposite relationship was found. Similar relationships have been reported between heart rate reactivity and resting total cholesterol in hypertensive men (Jorgensen, 19881, and between resting levels of the ratio of total/HDL cholesterol and catecholamine reactivity in post-myocardial infarction men (Fredrikson & Blumenthal, 1988). No published reports of young, healthy individuals have identified a relationship between exaggerated reactivity and elevated resting lipid levels, and we have been unable to establish such an association among healthy subjects in our laboratory. This suggests that high resting levels of lipids (as might be seen in high risk individuals) may potentiate acute reactivity to stressors. Support for this

30


research

notion comes from animal studies, where elevated total serum cholesterol has been shown to augment the response to vasoconstrictor stimuli (Heistad, Armstrong, Marcus, Piegors & Mark, 1984; Rosendorf, Hoffman, Verrier, Rouleau & Boerboom, 19811, and to upregulate beta-adrenergic receptor functioning (McMurchie & Patten, 1988). Alternatively, the finding could simply be reflecting the fact that high risk individuals who are particularly reactive have elevated lipid levels by virtue of having advanced disease. Stated differently, the elevation in lipids and reactivity may both be a function of the disease process. Conclusions The review of individual differences suggests that several individual characteristics may be related to an atherogenic lipid profile. Individuals who evidence high levels of autonomic or neuroendocrine reactivity to stressors are more likely to show elevations in resting levels of serum lipids. Likewise, Type A behavior, and especially aspects related to hostility/aggressiveness and drive, are related to elevated lipid levels. A personality style characterized by adherence to social norms, rigidity, and use of avoidance strategies to deal with negative emotions also appears to increase risk. Individuals who show greater reliance on environmental or external cues for information are more likely to show elevations in serum lipids. Finally, elevated resting total cholesterol or the ratio of total/HDL cholesterol is positively related to increased cardiovascular and neuroendocrine response to acute stress in persons at risk for CHD or with established disease, but the direction of causation is still undetermined. These differences may all be linked to common physiological mechanisms which predispose toward elevations in serum lipids, i.e. increased resting or stress-related activity of autonomic nervous and neuroendocrine systems. Each of these individual differences may have direct effects on lipids, or may be associated with a change in behaviors (e.g. diet, activity, smoking) which influence lipids. For example, social support may act to buffer against stress effects, by altering perceptions of stress. Men and women may differ physiologically in their responses to stress, and these differences may also be apparent at the level of lipids and lipoproteins. High risk individuals may be particularly susceptible to stress-induced alterations in lipid metabolism. We should point out that, however promising consideration of these individual differences may be in understanding the interaction between psychological variables and lipids, the findings of these studies are not uniform and no definitive conclusions can be stated at this time. Unfortunately, the existing studies vary considerably in the rigor which they applied to assessing the confounding influences of diet, activity, smoking and weight, and few have systematically set out to study specifically the effects of individual differences


on lipids. The handful of studies that examined whether differences interacted with a stressor to influence lipids have that the manner in which psychological influences impact lipoproteins is a complex one, perhaps operating through an of psychological, behavioral and physiological mechanisms.

Mechanisms

31

research

key individual demonstrated on lipids and intricate maze

of action: multiple pathways

The precise mechanism or mechanisms by which psychological factors produce elevations in lipids and lipoproteins are currently unknown and virtually untested. Figure 1 illustrates a simplified model describing several

PSYCHOLOGICAL

FACTORS

t

t d

STRESS (episodic, chronic, acute)

SENSITIVE GROUPS (repressors, men, hostile Type A, poor capers, low social support)

4

I

I

I

t

h

STIMULATE ADIPOSE 0 RECEPTORS 1 LIPOPROTEIN LIPASE I HEPATIC TRIGLYCERIDE LIPASE

I

CHANGES

Fig. 1. The impact

IN LIPIDS, LIPOPROTEINS

of psychological

factors

AND APOLIPOPROTEINS

on lipids and lipoproteins.

I

32


research

pathways by which behavioral stress and individual difference variables might impact on the relationship between psychological factors and lipid levels. Regarding the specific effects of stress on lipids, lipoproteins, and apolipoproteins (pathway a), individual variation in neuroendocrine activity along the sympathetic-adrenal-medullary (SAM) axis in response to acute or chronic stress is likely to play a role in modulating lipid and lipoprotein metabolism (pathway c). For example, activity along the SAM axis, characterized by secretion of the catecholamines epinephrine and norepinephrine, is increased during a variety of stressors. These catecholamines in particular are important in the mobilization and metabolism of lipids and lipoproteins. Epinephrine may induce release of FFA indirectly by increasing blood flow through adipose tissue and directly by stimulating adipose beta, receptors (Dimsdale, Herd & Hartley, 1983; Have1 & Goldfien, 1959; Shafrir, Sussman & Steinberg, 1959). Increases in circulating FFA due to stress-induced lipolysis may trigger production of triglyceride-rich VLDL by the liver leading to hypertriglycerdemia. Efficient VLDL catabolism may in turn increase levels of circulating LDL cholesterol. Norepinephrine can induce lipolysis by stimulating beta, receptors in adipose tissue and by decreasing insulin levels (Hjemdahl & Linde, 1983). Norepinephrine may also diminish the activity of lipoprotein lipase (Miller, Gorski, Oscai & Palmer, 1989) in turn diminishing clearance of triglycerides and lowering levels of HDL cholesterol. In addition, norepinephrine decreases hepatic triglyceride lipase activity (Jansen & Hulsmann, 1985; Schoonderwoerd, Hulsman & Jansen, 1984) which could increase plasma levels of very low density lipoproteins, intermediate density lipoproteins and LDL. Activation of the hypothalamic-pituitary-adrenocortical system during stress, characterized by secretion of cortisol, may also play a role in mobilization of lipids and lipid metabolism. Infused cortisol results in FFA and glycerol elevations (Mischke, Ebers, Boisch & Tamm, 1974). Adrenocorticoids and FFA increase activity of HMG-CoA reductase in the liver (Cavenee & MeInykovychl979) stimulating synthesis of cholesterol. The effects of fatty acids may interact with adrenocorticoids to stimulate cholesterol production (Troxler & Schwertner, 1985). Moreover, adrenocorticoids may depress lipoprotein lipase activity (Jansen & Hulsman, 1985), ultimately leading to lower levels of HDL cholesterol. Regarding the effects of individual difference variables (pathway b), it is clear that psychological factors might impact on lipids and lipoproteins through differences in health behaviors (pathway f). For example, adequate social support networks might enhance health behaviors and lead to a more favorable lipid profile. Alternatively, these individual differences might impact on physiologic adjustments to stress (pathway d). For example, it has been suggested that hostile Type A individuals respond to behavioral stress with larger magnitude elevations in blood pressure, catecholamines and heart


research

33

rate (Suarez et al., 1991) than do other individuals. Other, constitutional/ genetic variables associated with individual differences in psychological function might also directly impinge on lipid levels (pathway il. We have included another pathway in the model which illustrates potential interactions among health behaviors and reactivity to stressors (pathway g). By way of example, we know that cigarette smoking (Perkins, Epstein, Jennings & Stiller, 1986) and physical fitness (Holmes & McGilley, 19871 can affect cardiovascular reactivity to stress, and these behaviors may also modulate lipid stress responses. It is also possible that other changes in health behaviors that might occur as a function of stress, such as diet and sleep, interact with stress responsiveness to affect lipids indirectly. For example, exposure to a chronic auditory stressor increased total serum cholesterol more in rabbits who were fed a cholesterol-rich diet than in rabbits fed a stock diet (Friedman, Byers & Brown, 1967). More recently, administration of norepinephrine raised LDL cholesterol in cholesterol-fed rabbits, but not in rabbits fed a normal diet (O’Donnell et al., 1988). Thus, adrenergic and behavioral factors may interact to alter lipoprotein concentration and metabolism. Finally, it is important to note that some or all of these pathways may be active simultaneously and to varying degrees. One study in particular illustrates this point. Mattiasson et al., (1990) found that, among male shipyard workers, the threat of unemployment increased levels of total serum cholesterol, as well as the incidence of sleep disturbance, significantly. In univariate analyses, stress-associated changes in weight, hemoglobin, heart rate, blood pressure, ratings of muscle tension and sleep disturbance correlated significantly with change in total cholesterol. Thus, this study illustrates the combined effect of psychological stress (pathway a), physiological consequences (reactivity) to that stress (pathway c), and changes in health behaviors as a result of that stress (pathways e and g). Although clearly not comprehensive, we wish to illustrate with this model both the complexities involved in this type of research, as well as the varied avenues of research that are yet to be explored in this area. It is essential that psychologists working in this area become even more physiologically sophisticated with regard to lipid metabolism, in order to fully understand the relationships between psychological factors and lipids and lipoproteins.

Conclusions Ten years ago, a review of the literature examining lipid changes during stressful experiences led the authors to conclude that there was sufficient evidence to believe that psychological stress can result in significant elevations in FFA and total cholesterol (Dimsdale and Herd, 1982). Since that

34


time, several dozen additional studies have examined this further by extending the types of stress examined; by increasing the number of indices of lipid metabolism measured; and by examining other physiological changes that occur concomitant with lipid changes. A separate but related literature has examined psychological and constitutional differences that influence lipid levels at rest and that may modulate lipid responses to stress. In this review, we examine all of these additional studies, and conclude that, while there is little evidence to support the notion that mild forms of chronic or episodic stress are associated with alterations in lipids and lipoproteins, more severe forms of real or perceived stress do appear to alter lipid levels. Additionally, acute laboratory stress is frequently associated with short-term alterations in lipids and lipoproteins. Finally, individual differences in several psychological parameters appear to be associated with differing lipid levels, although the direction of causation is unknown. Some caveats with this line of research should be noted. First, although it is clear that the most consistent finding in this literature is that acute stress is associated with increases in FFA levels, it remains to be shown that the FFA response is responsible for sustained elevations in resting lipids and, more importantly, increased risk for CHD. Stated differently, there is no direct evidence that the stress-induced metabolic excess of circulating FFA has any important consequences. It is possible that, for most individuals, temporary perturbations in this system are easily and quickly accommodated by homeostatic processes so that there is very little net change in the level of lipids farther along in the metabolic pathway. Even if this is true, however, it is equally possible that these normally strong homeostatic forces could be overwhelmed in certain individuals and under certain conditions. Second, and related to the first point, questions remain concerning the meaning of these studies in terms of showing a relationship between response to stress on the one hand, and important and sustained elevations in resting lipids and lipoproteins on the other. Third, although several of the studies suggest that there are direct, acute effects of stress on serum lipids, we have not yet demonstrated a plausible mechanism whereby these effects might occur. In normal persons, the biological half-life of LDL cholesterol is 3-5 days, and the half-life of HDL cholesterol is 5-7 days. Furthermore, pools of LDL or HDL cholesterol are not sequestered in the body. Thus, it is extremely unlikely that the increased lipoprotein levels observed during a short-term perturbation such as mental arithmetic are a result of increased synthesis of circulating lipoproteins. While it is more likely that changes in lipids during short-term stress are reflecting alterations in plasma volume, several studies which have corrected stress-associated lipid levels for changes in hematocrit (an estimate of plasma volume) still found that acute stress resulted in significant changes in lipids and lipoproteins (Davis & Matthews, 1990; Matthews et al., 1991; Stoney et


research

35

al., 1988). It is critically important that we gain a better understanding of the biological mechanisms which effect changes in lipids, either as a function of, or concurrent with, behavioral stress. Some studies have made contributions towards this end. For example, monitoring multiple hormonal changes concurrent with changes in lipids (e.g. O’Donnell et al., 1987, Stoney et al., 1988) allows us to understand further the biological underpinnings of the stresslipid relationship. Fourth, some of the failure to find significant alterations in lipids and lipoproteins may be a function of our incomplete understanding of the time course of changes that we might expect with stress. For example, while laboratory stressors over the course of 5-10 min can result in changes in some lipid parameters, it is unlikely that the same mechanisms are responsible for changes in lipids that may occur during chronic stress, since the time parameters of these situations differ widely. Failure to note changes during stress may be a function of sampling the system at the wrong time. It is clear that there is enormous interest in examining the impact of psychological factors on lipids and lipoproteins. To date, there is good evidence that some, but by no means all, types of stress can effect changes in lipids and lipoproteins, but the mechanisms responsible for such changes are currently unknown. It is our belief that future work in this area should concentrate on understanding these mechanisms.

Acknowledgement

This work was supported in part by grants from the National Heart Lung and Blood Institute: #HL46611 (Dr. Niaura), and #HL45855 (Dr. Stoney). We thank Lori Krawetz and Linda Bausserman, Ph.D. for help in preparing the manuscript.

References Almada, S.J., Zonderman, A.B., Shekelle, R.B., Dyer, A.R., Daviglus, M.L., Costa, P.T., Jr., & Stamler, J. (1991). Neuroticism and cynicism and risk of death in middle-aged men: The Western Electric Study. Psychosomatic Medicine, 53, 165-175. Arnetz, B.B., & Fjellner, B. (1986). Psychological predictors of neuroendocrine responses to mental stress. Journal of Psychosomatic Research, 30 (3), 297-305. Arnetz, B.B., Fjellner, B., Eneroth, P., & Kallner, A. (1985). Stress and psoriasis: psycho endocrine and metabolic reactions in psoriatic patients during standardized stressor exposure. Psychosomatic Medicine, 47 (61, 528-541. Arntzenius, A.C., Kromhout, D., Barth, J.D., Reiber, J.H.C., Bruschke, A.V.G., Buis, B.,van Gent, C.M., Kempen-voogd, N., Strikwerda, S., & van der Velde, E.A. (1985). Diet, lipoproteins, and the progression of coronary atherosclerosis. New England Journal of Medicine, 312, 805-811.

36


Asendorpf, J., & Scherer, K. (1983). The discrepant repressor: Differentiation between low anxiety, high anxiety, and repression of anxiety by autonomic-facial-verbal patterns of behavior. Journal of Personality and Social Psychology, 45, 1334-1346. Bijlani, R.L., Gandhi, B.M., & Tandon, B.N. (1983). Effect of examination stress on serum lipid profile. Tropical Gastroenterology, 4 (3), 168-170. Bijlani, R.L., Sud, S., Gandhi, B.M., & Tandon, B.N. (1986). Relationship of examination stress to serum lipid profile. Indian Journal of Physiology and Pharmacology, 30 (l), 22-30. Balm-Audorff, U., Schwiimmle, J., Enlenz, K., & Kaffarnik, H. (1989). Plasma level of catecholamines and lipids when speaking before an audience. Work & Stress, 3 (3), 249-253. Brand, R.J. (1978). Coronary-prone behavior as an independent risk factor for coronary heart disease. In T.M. Dembroski, SM. Weiss, J.L. Shields, S.G. Haynes, & M. Feinleib (Eds.), Coronary-prone hehauior. New York: Springer-Verlag. Breslow, J.L. (1991). Lipoprotein transport gene abnormalities underlying coronary heart disease susceptibility. Annual Retiew of Medicine, 42, 3577371. Castelli, W.P., Doyle, J., Gordon, T., Hames, C.G., Hjortland, M., Hulley, S.B., Kagan, A. & Zukel, W.J. (1977). Alcohol and blood lipids: the Cooperative Lipoprotein Phenotyping Study. Lancet, 2, 153-155. Cavenee, W.K., & MeInykovych, G. (1979). Elevation of HeLa cell 3-hydroxy-3 methylglytaryl Co-enzyme A reductase activity by glucocorticoids: Possible relationship to the cell cycle. Journal of Cellular Physiology, 98, 199-2 11. Chesney, M.A., Sevelius, G., Black, G.W., Ward, M.M., Swan, G.E., & Rosenman, R.H. (1981). Work environment, type A behavior, and coronary heart disease risk factors. Juumal of Occupational Medicine, 23, 551-555. Cohen, J.B., & Reed, D. (1985). The type A behavior pattern and coronary heart disease among Japanese men in Hawaii. Journal of Behavioral Medicine, 8 (4), 3433352. Comens, P., Reed, D., & Mette, M. (1987). Physiologic responses of pilots flying high-performance aircraft. Aviation, Space, and Enncironmental Medicine, 58, 205-210. Cook, W., & Medley, D. (1954). Proposed hostility and pharasaic-virtue scales for the MMPI. Journal of Applied Psychology, 38, 414-418. Davis, M.C., & Matthews, K.A. (1990). Cigarette smoking and oral contraceptive use influence women’s lipid, lipoprotein, and cardiovascular response during stress. Health Psychology, 9 (6), 717-736. Diamond, E.L. (1982). The role of anger and hostility in essential hypertension and coronary heart disease. Psychological Bulletin, 92, 419-433. Dimsdale, J.E., & Herd, J.A. (1982). Variability of plasma lipids in response to emotional arousal. Psychosomatic Medicine, 44, 413-430. Dimsdale, J.E., Herd, J.A., & Hartley, L.H. (1983). Epinephrine mediated increases in plasma cholesterol. Psychosomatic Medicine, 45, 227-232. Eaker, E.D., Abbott, R.D., & Kannel, W.B. (1989). Frequency of uncomplicated angina pectoris in type A compared with type B persons (the Framingham study). The American Journal of Cardiology, 63, 1042-1045. Flemenbaum, A., & Anderson, R.P. (1978). Field dependence and blood cholesterol: An expansion. Perceptual and Motor Skills, 46, 867-874. Flemenbaum, A., & Flemenbaum, E. (1975). Field dependence, blood uric acid and cholesterol. Perceptual and Motor Skills, 41, 135-141. Flynn, M.A., Anderson, A., Rutledge, M., Nolph, G.B., Krause, G., & Ellersieck, M.R.(1984). Eggs, serum lipids, emotional stress, and blood pressure in medical students. Archives of Enr~ironmental Health, 39 (2), 90-95. Fredrikson, M., & Blumenthal, J.A. (1988). Lipids, catecholamines, and cardiovascular responses to stress in patients recovering from myocardial infarction. Journal of Cardiopulmonary Rehahilitution, 12, 513-517.


37

Frick, M.H., Elo, O., Haapa, K., Heinonen, O.P., Heinsalmi, P., Helo, P., Huttunen, J.K., Kaitaniemi, P., Koskinen, P., Manninen, V., Mlenpla, H., Mllkonen, M., MBntPri, M., Norola, S., Pasternack, A., Pikkarainen, J., Romo, M., Sjoblom, T., & Nikkila, E.A. (1987). Helsinki Heart Study: Primary prevention trial with gemfibrozilin middle-aged men with dyslipidemia. New England Journal of Medicine, 317, 1237. Friedman, E.H., Hellerstein, H.K., Eastwood, G.L., & Jones, SE. (1968). Behavior patterns and serum cholesterol in two groups of normal males. The American Journal of the Medical Sciences, 255, 237-244. Friedman, M., Byers, S.O., & Brown, A.E. (1967). Plasma lipid responses of rats and rabbits to an auditoty stimulus. American Journal of Physiology, 212 (51, 1174-l 178. Friedman, M., Byers, S.O., Rosenman, R.H., & Elevitch, F.R. (1970). Coronary-prone individuals (Type A behavior pattern): Some biochemical characteristics. Journal of the American Medical Association, 222 (6), 1030-1037. Friedman, M., & Rosenman, R.H. (1959). Association of specific overt behavior pattern with blood and cardiovascular findings. Journal of the American Medical Association, 169 (12), 1286-1296. Friedman, M., Rosenman, R.H., & Byers, S. (1964). Serum lipids and conjunctival circulation after fat ingestion in men exhibiting type-A behavior pattern. Circulation, 29, 874-886. Friedman, M., St. George, S., Byers, S.O., & Rosenman, R.H. (1960). Excretion of catecholamines, 17 ketosteroids, 17 hydroxy-corticoids, and 5-hydroxy indole in men exhibiting a particular behavior pattern (A) associated with high incidence of clinical coronary artery disease. Journal of Clinical Investigation, 39, 758-764. Gallacher, J.E., Yarnell, J.W., & Butland, B.K. (1988). Type A behaviour and prevalent heart disease in the Caerphilly study: Increase in risk of symptom reporting? Journal of Epidemiology and Community Health, 42, 226-231. Garrity, T.F., Kotchen, J.M., McKean, H.E., Gurley, D., & McFadden, M. (1990). The association between type A behavior and change in coronary risk factors among young adults. American Journal of Public Health, 80, 1354-1357. Gill, J.J., Price, V.A., Friedman, M., Thoresen, C.E., Powell, L.H., Ulmer, D., Brown, B., & Drews, F.R. (1985). Reduction in type A behavior in healthy middle-aged American military officers. American Heart Journal, 110 (31, 503-514. Gillum, R.F., Taylor, H.L., Anderson, J., & Blackburn, H. (1981). Longitudinal study (32 years) of exercise tolerance, breathing response, blood pressure, and blood lipids in young men. Arteriosclerosis, 1 (6), 455-462. Goldstein, D.S., Dionne, R., Sweet, J., Gracely, R., Brewer, H.B., Jr., Gregg, R., Keiser, H.R. (1982). Circulatory, plasma catecholamine, cortisol, lipid, and psychological responses to a real-life stress (third molar extractions): Effects of diazepam sedation and of inclusion of epinephrine with the local anesthetic. Psychosomatic Medicine, 44 (3), 259-272. Gore, S. (1978). The effects of social support in moderating the health consequences of unemployment. Journal of Health and Social Behavior, 19, 157-165. Guilford, J.P., & Zimmerman, W.S. (1949). The Guilford-Zimmerman Temperament Suruey. Manual of instructions and interpretations. Beverly Hills, CA: Sheidan Supply Co. Harlan, W.R., Jr., Oberman, A., Mitchell, R.E., & Graybiel, A. (1967). Constitutional and environmental factors related to serum lipid and lipoprotein levels. Annals of Internal Medicine, 66 (3), 540-555. Havel, R.J., & Goldfien, A. (1959). The role of the sympathetic nervous system in the metabolism of free fatty acids. Journal of Lipid Research, I (11, 102-108. Hazzard, W.R. (1985). Atherogenesis: Why women live longer than men. Geriatrics, 40, 42. Heistad, D.D., Armstrong, M.L., Marcus, M.L., Piegors, D.J., & Mark, A.L. (1984). Augmented responses to vasoconstrictor stimuli in hypercholesterolemic and atherosclerotic monkeys. Circulation Research, 54, 71 l-718.

38


Hendrix, W.H., Ovalle, N.K., & Troxler, R.G. (1985). Behavioral and physiological consequences of stress and its antecedent factors. Journal of Applied Psychology, 71 (l), 188-201. Henrotte, J.G., Plouin, P.F., L&y-Leboyer, C., Moser, G., & Pineau, M. (1985). Blood and urinary magnesium, zinc, calcium, free fatty acids, and catecholamines in Type A and Type B subjects. Journal of the American College of Nutrition, 4, 165-172. Hjemdahl, P., & Linde, B. (1983). Influences of circulating NE and Epi on adipose tissue and vascular resistance and lipolysis in humans. American Journal of Physiology, 245, H447-H452. Hjemdahl, P., & Linde, B. (1985). Adrenergic control of blood flow and lipolysis in human adipose tissue. In H. Refsum & O.D. Mjos (Eds.), Alpha-adrenoceptor blockers in cardioeascular disease, pp. 151-164. London: Churchill Livingstone. Hollis, J.F., Connett, J.E., Stevens, V.J., & Greenlick, M.R. for the MRFIT Group (1990). Stressful life events, type A behavior, and the prediction of cardiovascular and total mortality over six years. Journal of Behavioral Medicine, 13 (3), 263-280. Holmes, D.S. & McGilley, B.M. (1987). Influence of a brief aerobic training program on heart rate and subjective response to a psychologic stressor. Psychosomatic Medicine, 49, 366-374. Howard, J.H., Cunningham, D.A., & Rechnitzer, P.A. (1976). Health patterns associated with type A behavior: A managerial population. Journal of Human Stress, 24-31. Howard, J.H., Cunningham, D.A., & Rechnitzer, P.A. (1986). Personality (hardiness) as a moderator of job stress and coronary risk in type A individuals: A longitudinal study. Journal of Behavioral Medicine, 9 (3), 229-244. Hubert, H.B., Eaker, E.D., Garrison, R.J., & Castelli, W.P. (1987). Life-style correlates of risk factor change in young adults: An eight-year study of coronary heart disease risk factors in the Framingham offspring. American Journal of Epidemiology, 125 (51, 812-831. Hulley, S.B., Cohen, R., & Widdowson, G. (1977). Plasma high-density lipoprotein cholesterol level: Influence of risk factor intetvention. Journal of the American Medical Association, 238, 2269-2271. Jansen, H., & Hulsmann, W.C. (1985). Enzymology and physiological role of hepatic lipase. Biochemical Society Transactions, 13, 24-26. Jenkins, C.D., Hames, C.G., Zyzanski, S.J., Rosenman, R.H., & Friedman, M. (1969). Psychological traits and serum lipids. Psychosomatic Medicine, 32(2), 115-128. Jenkins, C.D., Rosenman, R.H., & Friedman, M. (1966). Components of the coronary-prone behavior pattern: Their relation to silent myocardial infarction and blood lipids. Journal of Chronic Diseases, 19, 599-609. Joborn, H., Hjemdahl, P., Larsson, P.T., Lithell, H., Olsson, G., Wide, L., Bergstrom, R., & Ljunghall, S. (1990). Effects of prolonged adrenaline infusion and of mental stress on plasma minerals and parathyroid hormone. Clinical Physiology, 10, 37-53. Jorgensen, R.S., Nash, J.K., Lasser, N.L., Hymowitz, N., & Langer, A.W. (1988). Heart rate acceleration and its relationship to total serum cholesterol, triglycerides, and blood pressure reactivity in men with mild hypertension. Psychophysiology, 25 (l), 39-44. Kasl, S.V., Cobb, S., & Brooks, G.W. (1968). Changes in serum uric acid and cholesterol levels in men undergoing job loss. Journal of the American Medical Association, 206 (I), 1500-1507. Keith, R.A., Lown, B., & Stare, F.J. (1965). Coronary heart disease and behavior patterns. Psychosomatic Medicine, 27, 424-434. Kemmer, F.W., Bisping, R., Steingriiber, H., Baar, H., Hardtmann, F., Schlaghecke, R., & Berger, M. (1986). Psychological stress and metabolic control in patients with type I diabetes mellitus. The New England Journal of Medicine,314 (ll), 1078-1084. King, A.C., Albright, CL., Barr Taylor, C., Haskell, W., & DeBusk, R.F. (1986). The repressive coping style: A predictor of cardiovascular react&y and risk. Presented at the Seventh Annual Meeting of the Society of Behavioral Medicine, San Francisco, CA, March. King, A.C., Albright, CL., Taylor, C.B., Haskell, W.L., & DeBusk, R.F. (1990). The relationship between repressive and defensive coping styles and blood pressure responses in healthy, middle-aged men and women. Journal of Psychosomatic Research, 34, 461-471.


39

Kirkeby, O.J. Risoe, C., & Kirkeby, K. (1984). Serum cholesterol and thyroxine in young women during mental stress. Experimental and Clinical Endocrinology, 83 (3), 361-363. Kornitzer, M., Dramaix, M., DeBacker, G., & Thilly, C. (1977). The Belgian multifactor preventive trial in CVD (II): Cholesterolemia and psycho-socio-biological variables. Heart Bulletin, 8, 147-154. Larsson, P.T., Martinsson, A., Olsson, G., & Hjemdahl, P. (1989). Altered adrenoceptor responsiveness during adrenaline infusion but not during mental stress: Differences between receptor subtypes and tissues. British Journal of Clinical Pharmacology, 28, 663-674. Lipid Research Clinics Coronary Primary Prevention Trial results, I (1984): Reduction in incidence of coronary heart disease. Journal of the American Medical Association, 251, 351-364. Lovallo, W.R., Wilson, M.F., Pincomb, G.A., Edwards, G.L., Tompkins, P., & Brackett, D.J. (1985). Activation patterns to aversive stimulation in man: Passive exposure versus effort to control. Psychophysiology, 22 (3), 283-291. Lovallo, W.R., & Pishkin, V. (1980). A psychophysiological comparison of type A and B men exposed to failure and uncontrollable noise. Psychophysiology, 17 (I), 29-36. Lundberg, U., Fredrikson, M., Wallin, L., Melin, B., & Frankenhaeuser, M. (1989). Blood lipids as related to cardiovascular and neuroendocrine functions under different conditions in healthy males and females. Pharmacology Biochemistry & Behacior, 33, 381-386. Lundberg, U., Hedman, M., Melin, B., & Frankenhaeuser, M. (1989). Type A behavior in healthy males and females as related to physiological reactivity and blood lipids. Psychosomatic Medicine, 51, 113-122. Manninen, V., Elo, M.O., Frick, M.H., Haapa, K., Heinonen, O.P., Heinsalmi, P., Helo, P., Huttunen, J.K., Kaitiemi, P., Koskinen, P., Maenpaa, H., Miilkonen, M., Mantari, M., Norola, S., Pasternack, A., Pikkarainen, J., Romo, M., Sjoblom, T., & Nikkilii, E.A. (1988). Lipid alterations and decline in the incidence of coronary heart disease in the Helsinki Heart Study. Journal of the American Medical Association, 260, 641-650. Manuck, S.B., Kaplan, J.R., & Matthews, K.A. (1986). Behavioral antecedents of coronary heart disease and atherosclerosis. Arteriosclerosis, 6, 2- 14. Matthews, K.A., Davis, M.C., Stoney, C.M., Owens, J.F., & Caggiula, A.R. (1991). Does the gender relevance of the stressor influence sex differences in psychophysiological responses? Health Psychology, 10 (2), 112-120. Mattiasson, I., Lindglrde, Nilsson, J.A., & Theorell, T. (19901. Threat of unemployment and cardiovascular risk factors: Longitudinal study of quality of sleep and serum cholesterol concentrations in men threatened with redundancy. British Medical Journal, 302, 461-466. Maxwell, V.B., Crump, J.H., & Thorp, J. (1983). The measurement of risk indicators for coronary heart disease in air traffic control officers: A screening study in a healthy population. Aviation, Space, and Enoironmental Medicine, 54 (3), 246-249. McCann, B.S., Warnick, G.R., & Knopp, R.H. (1990). Changes in plasma lipids and dietary intake accompanying shifts in perceived workload and stress. Psychosomatic Medicine, 52, 97-108. McCranie, E.W., Simpson, M.E., & Stevens, J.S. (1981). Type A behavior, field dependence, and serum lipids. Psychosomatic Medicine, 43 (2), 107-116. McGough, W.E., Silverman, A.J., & Bogdonoff, M.D. (19651. Patterns of fat mobilization in field-dependent and field-independent subjects. Psychosomatic Medicine, 27 (3), 245-256. McKinney, M.E., McIlvain, H.E., Hofschire, P.J., Collins, R.E., Somers, J.A., Ruddel, H., Buell, J.C., & Eliot, R.S. (1987). Psychophysiologic aspects in essential hypertension. Journal of Human Hypertension, 1, 137-145. McMurchie, E., & Patten, G. (1988). Dietary cholesterol influences cardiac P-adrenergic receptor adenylate cyclase activity in the marmoset monkey by changes in membrane cholesterol status. Biochemical and Biophysical Acta, 942, 324-332.

40


Miller, W.C., Gorski, J., Oscai, L.B., & Palmer, W.K. (1989). Epinephrine activation of heparin nonreleasable lipoprotein lipase in three skeletal muscle fiber types of the rat. Biochemistry & Biophysics Research Communications, 164, 615-619. Mischke, W.G.S., Ebers, S., Boisch, K.H., & Tamm, J. (1974). The influence of intravenously administered cortisol on various parameters of fat and carbohydrate metabolism in blood plasma of human beings. Acta Endrocrinologia Supplementurn, (186), l-45. Netterstrom, B., Danborg, L., & Olesen, H. (1988). Glycated hemoglobin as a measure of physiological stress. Behavioral Medicine, 13-16. Niaura, R., & Herbert, P. (1991). Hostility and blood lipids in healthy adults. Presented at the 12th Annual Meeting of the Society of Behavioral Medicine, Washington, DC, March. Niaura, R., Herbert, P., McMahon, N., & Sommerville, L. (in press). Repressitbe coping and blood lipids in men and women. Psychosomatic Medicine. Niaura, R., Herbert, P.N., Saritelli, A., Goldstein, M., Flynn, M., Follick, M., Gorkin, L., & Ahern, D. (1991). Lipid and lipoprotein response to episodic occupational and academic stress. Archiues of Internal Medicine, 151, 2172-2179. O’Donnell, L., O’Meara, N., Owens, D., Johnson, A., Collins, P., & Tomkin, G. (1987). Plasma catecholamines and lipoproteins in chronic psychological stress. Journal of the Royal Society of Medicine, 80, 339-342. O’Donnell, L., Owens, D., McGee, C., Devery, R., Hession, P., Collins, P., Johnson, A., & Tomkin, G. (1988). Effects of catecholamines on serum lipoproteins of normally fed and cholesterol-fed rabbits. Metabolism, 37, 910-915. Ohara, K., Klag, M.J., Sakai, Y., Whelton, P.K., Itoh, I., & Comstock, G.W. (1991). Factors associated with high density lipoprotein cholesterol in Japanese and American telephone executives. American Journal of Epidemiology, I34 (21, 137-148. Orth-Comer, K., & UndCn, A.L. (1990). Type A behavior, social support, and coronary risk: Interaction and significance for mortality in cardiac patients. Psychosomatic Medicine, 52, 59-72. Orth-Gamer, K. (1983). Intervention on coronary risk factors by adapting a shift work schedule to biologic rhythmicity. Psychosomatic Medicine, 45 (5), 407-415. Perkins, K.A., Epstein, L.H., Jennings, J.R., & Stiller, R. (1986). The cardiovascular effects of nicotine during stress. Psychopharmacology, 90, 373-378. Pieper, C., LaCroix, A.Z., & Karasek, R.A. (1989). The relation of psychosocial dimensions of work with coronary heart disease risk factors: A meta-analysis of five United States data bases. American Journal of Epidemiology, 129 (3), 483-494. Pincomb, G.A., Lovallo, W.R., Passey, R.B., Brackett, D.J., & Wilson, M.F. (1987). Caffeine enhances the physiological response to occupational stress in medical students. Health Psycholom, 6 (2), 101-112. Rai, R.M., Singh, A.P., Upadhyay, T.N., Patil, S.K.B., & Nayar, H.S. (1981). Biochemical effects of chronic exposure to noise in man. International Archives of Occupational and Enuironmental Health, 48, 331-337. Reed, D.M., LaCroix, A.Z., Karasek, R.A., Miller, D. & MacLean, C.A. (1989). Occupational strain and the incidence of coronary heart disease. American Journal of Epidemiology, 129 (3), 495-502. Rosendorf, C., Hoffman, J., Verrier, E., Rouleau, J., Boerboom, L. (1981). Cholesterol potentiates the coronary artery response to norepinephrine in anesthesized and conscious dogs. Circulation Research, 48, 320-328. Rosenman, R.H., & Friedman, M. (1961). Association of specific behavior pattern in women with blood and cardiovascular findings. Circulation, 24, 1173-1184. Rosenman, R.H., & Friedman, M. (1963). Behavior patterns, blood lipids, and coronary heart disease. Journal of the American Medical Association, I84 (12), 112-l 16. Scherwitz, L., Perkins, L., Chesney, M., Hughes, G., Sidney, S., & Manolio, T. (1991). CookMedley hostility and detrimental health behaciors in young adults: The CARDIA study. Pre-


research

41

sented at the 12th Annual Meeting of the Society of Behavioral Medicine, Washington, DC, March. Schwaberger, G. (1987). Heart rate, metabolic and hormonal responses to maximal psycho-emotional and physical stress in motor car racing drivers. International Archiues of Occupational and Environmental Health, 59, 579-604. Schoondenvoerd, K., Hulsmann, W.C., & Jansen, H. (1984). Regulation of liver lipase II. Involvement of the alpha-l receptor. Biochemical and Biophysical Acta, 795, 481-486. Sedgwick, A.W., Davidson, A.H., Taplin, R.E., & Thomas, D.W. (1981). A pilot study of some associations between behavioral stressors and physiological processes in healthy men. European Journal of Applied Physiology and Occupational Physiology, 46, 409-421. Segers, M.J., & Mertens, C. (1976). Relationships between anxiety, depression self-ratings and CHD risk factors among obese, normal and lean individuals. Journal of Psychosomatic Research, 20, 25-35. Shafrir, E., Sussman, K.E., & Steinberg, D. (1959). The nature of the epinephrine-induced hyperlipidemia in dogs and its modification by glucose. Journal of Lipid Research, 1, 109-117. Shekelle, R.B., Gale, M., Ostfeld, A.M., & Paul, 0. (1983). Hostility, risk of coronary heart disease, and mortality. Psychosomatic Medicine, 4.5 (2), 109-114. Shekelle, R.B., Schoenberger, J.A., & Stamler, J. (1976). Correlates of the JAS type A behavior pattern score. Journal of Chronic D&eases, 29, 381-394. Sibai, A.M., Armenian, H.K., & Alam, S. (1989). Wartime determinants of arteriographically confirmed coronary artery disease in Beirut. American Journal of Epidemiology, 130 (4), 623-631. Siegrist, J., Matschinger, H., Cremer, P., & Seidel, D. (1988). Atherogenic risk in men suffering from occupational stress. Atherosclerosis, 69, 211-218. Simon, J., Krugej, E., &arc, V., & Kiiiek, M. (1983). Correlation of A/B behaviour pattern, alcohol intake, HDL-cholesterol and serum magnesium levels in middle-aged men. Actioitas Nervosa Superior, 25, 105-107. Sloane, R.B., Habib, A., Eveson, M.D., & Payne, R.W. (1961). Some behavioral and other correlates of cholesterol metabolism. Journal of Psychosomatic Research, 5, 183-186. Smoak, B.L., Norton, J.P., Ferguson, E.W., & Deuster, P.A. (1990). Changes in lipoprotein profiles during intense military training. Journal of the American College of Nutrition, 9 (6), 567-572. Sorensen, G., Pirie, P., Folsom, A., Luepker, R., Jacobs, D., & Gillum, R. (1985). Sex differences in the relationship between work and health: The Minnesota heart survey. Journal of Health and Social Behavior, 26,379-394. Spence, D., Manuck, S.B., Munoz, C., Cheung, H., Huff, M., Dennis, B., & Borkowski, K. (1990). Hemodynamic and endocrine effects of mental stress in untreated borderline hypertension. American Journal of Hypertension, 3, 859-862. Sprafka, J.M., Folsom, A.R., Burke, G.L., Hahn, L.P., & Pirie, P. (1990). Type A behavior and its association with cardiovascular disease prevalence in blacks and whites: The Minnesota Heart Survey. Journal of Behavioral Medicine, 13 (l), 1-13. Stamler, J., Wentworth, D., & Neaton, J.D., for the MRFIT Research Group (1986). Is relationship between serum cholesterol and risk of premature death from coronary heart disease continuous and graded? Findings in 356,222 primary screenees of the Multiple Risk Factor Intervention Trial (MRFIT). Journal of the American Medical Association, 256, 2823-2828. Stoney, C.M., Matthews, K.A., McDonald, R.H., & Johnson, C.A. (1988). Sex differences in lipid, lipoprotein, cardiovascular, and neuroendocrine responses to acute stress. Psychophysiology, 25 (61, 645-656. Stoney, C.M., Owens, J.F., Matthews, K.A., Davis, M.C., & Caggiula, A. (1990). Influences of the normal menstrual cycle on physiologic functioning during behavioral stress. Psychophysiology, 27 (2), 125-135.

42


research

Suarez, E.C., Williams, R.B., Jr., Kuhn, C.M., Zimmerman, E.H., & Schanberg, S.M. (1991). Biobehavioral basis of coronary-prone behavior in middle-aged men. Part II: Serum cholesterol, the type A behavior pattern, and hostility as interactive modulators of physiological reactivity. Psychosomatic Medicine, 53, 528-537. Takeshima, T., Takao, Y., Urakami, K., Nishikawa, S., & Takahashi, K. (1989). Muscle contraction headache and migraine. Cephafalgia, 9, 7-13. Theorell, T., Hamsten, A., de Faire, U., Orth-Gamer, K., & Perski, A. (1987). Psychosocial work conditions before myocardial infarction in young men. International Journal of Cardiology,15, 33-46. Thomas, C.B., Ross, D.C., & Duszynski, E.R. (1975). Youthful hypercholesteremia: Its associated characteristics and role in premature myocardial infarction. The Johns Hopkins Medical Journal, 136, 193-208. Thomas, P.D., Goodwin, J.M., & Goodwin, J.S. (1985). Effect of social support on stress-related changes in cholesterol level, uric acid level, and immune function in an elderly sample. American Journal of Psychiatry, 142 (6), 7355737. Timio, M., Verdecchia, P., Venanzi, S., Gentili, S., Ronconi, M., Francucci, B., Montanari, M., & Bichisao, E. (1988). Age and blood pressure changes: A 20-year follow-up study in nuns in a secluded order. Hypertension, 12 (4), 457-461. Trevisan M., Celentano, E., Meucci, C., Farinaro, E., Jossa, F., Krogh, V., Giumetti, D., Panico, S., Scottoni, A., & Mancini, M. (1986). Short-term effect of natural disasters on coronary heart disease risk factors. Arteriosclerosis, 6 (5), 491-494. Trevisan, M., Tsong, Y., Stamler, J., Tokich, T., Mojonnier, L., Hall, Y., Cooper, R., & Moss, D. (1983). Nervous tension and serum cholesterol: Findings from the Chicago coronary prevention evaluation program. Journal of Human Stress, I, 12-16. Troxler, R.G., & Schwertner, H.A. (1985). Cholesterol, stress, lifestyle, and coronary heart disease. Aviation, Space, and Environmental Medicine, July, 660-665. van Doornen, L.J.P. (1980). The coronary risk personality: Psychological and psychophysiological aspects. Psychotherapy and Psychosomatics, 34, 204-215. van Doornen, L.J.P., & van Blokland, R.W. (1987). Serum-cholesterol: Sex specific psychological correlates during rest and stress. Journal of Psychosomatic Research, 31 (2), 239-249. van Doornen, L.J.P., & van Blokland, R.W. (1989). The relation of type A behavior and vital exhaustion with physiological reactions to real life stress. Journal of Psychosomatic Research, 33 (6), 715-725. Villani, R.G., & Singer, G. (1991). Prevention of arousal-induced hyperlipidemia by glucose ingestion. Psychosomatic Medicine, 53, 557-565. Wahl, P., Walden, M.S., Knopp, R., Hoover, J., Wallace, R., Heiss, G., & Rifkind, B. (1983). Effect of estrogen/progestin potency on lipid/lipoprotein cholesterol. New England Journal of Medicine, 308, 862-867. Watkins, P.L., Fisher, E.B., Southard, D.R., Ward, C.H., & Schechtman, K.B. (1989). Assessing the relationship of type A beliefs to cardiovascular disease risk and psychosocial distress. Journal of Psychopathology and Behavioral Assessment, 11 (1) 113-125. Warrenburg, S., Levine, J., Schwartz, G.E., Fontana, A.F., Kerns, R.D., Delaney, R., & Mattson, R. (1989). Defensive coping and blood pressure reactivity in medical patients. Journal of Behavioral Medicine, 12 (51, 407-424. Webster, I.A., Porritt, D.W., & Brennan, P.J. (1983). Reported health, life-style and occupational stress in prison officers. Community Health Studies, 7 (3), 266-277. Weidner, G., Sexton, G., McLellarn, R., Connor, S.L., & Matarazzo, J.D. (1987). The rote of type A behavior and hostility in an elevation of plasma lipids in adult women and men. Psychosomatic Medicine, 49 (21, 136-145. Weinberger, D.A. (1991). Repressiue control of emotion: Implications for health. Presented at the American Psychological Association Annual Convention, San Francisco, CA, August.

R. Niaura et al. / L,ipids in psychological research

43

Wingard, D.L. (1982). The sex differential in mortality rates: Demographic and behavioral factors. American Journal of Epidemiology, 115, 206-216. Wingard, D.L., Suarez, L., & Barrett-Connor, E. (1983). The sex differential in mortality from all causes and ischemic heart disease. American Journal of Epidemiology, 117, 165-172. Wood, P.D., Haskell, W., Klein, H., Lewis, S., Stern, M.P., & Farquhar, J.W. (1976). The distribution of plasma lipoproteins in middle-aged male runners. Metabolism, 25, 1249-1257.

The last decade in ecological climate change impact research: where are we now?

Dopamine uptake: a review of progress in the last decade.

Oral clefting in china over the last decade: 205,679 patients.

A scoping review protocol to map the research foci trends in tobacco control over the last decade.

Interview: Cancer pain management: the last decade and looking forward.

Evanescent wave fluorescence biosensors: Advances of the last decade.

Australasian nutrition research for prevention and management of child obesity: innovation and progress in the last decade.

Green tea and anticancer perspectives: updates from last decade.

Anaesthesia Techniques for Caesarean Operations: Retrospective Analysis of Last Decade.

The first decade of organic spintronics research.

A decade of AIDS research.

The Surgical Management of Klatskin Tumours: Has Anything Changed in the Last Decade?

Trends in Diabetes Incidence in the Last Decade Based on Korean National Health Insurance Claims Data.

How did hepatitis B virus effect the host genome in the last decade?

Accelerated freshening of Antarctic Bottom Water over the last decade in the Southern Indian Ocean.

The Ferrier Lecture, 1974. Body temperature and fever: changes in our views during the last decade.

Changes over the last decade in carotid atherosclerosis in patients with end-stage kidney disease.

Changes in chemotherapy usage and outcome of early breast cancer patients in the last decade.

Changes in pelvic organ prolapse surgery in the last decade among United States urologists.

Improved pregnancy outcome in epileptic women in the last decade: relationship to maternal anticonvulsant therapy.

The incidence and beta-lactam resistance of Proteus vulgaris in hospital infections: the last decade.

In vivo toxicity studies of fusarium mycotoxins in the last decade: a review.

Impact of Brazilian papers in cardiology and cardiovascular sciences in the last decade.

Menopausal hormone therapy use in 17 European countries during the last decade.