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【摘要】
Objective- We examined the Type A behavior across developmental periods as a predictor of adult carotid artery intima-media thickness (IMT).
Methods and Results- In this prospective cohort study of 408 men and 606 women, socioeconomic background and biological risk factors of participants were assessed at baseline at age 6 to 18 years of age, Type A behavior (Hunter-Wolf A-B Rating Scale) at the 6-, 9-, and 21-year follow-ups (subjects being 12 to 24, 15 to 27, and 27 to 39 years, respectively), and carotid IMT, adulthood socioeconomic situation, and biological risk factors at the 21-year follow-up when participants were at age 27 to 39 years of age. In men, the eagerness-energy component of Type A behavior, measured at any time point, was associated with thicker carotid IMT ( P <0.008, P <0.04, P <0.03, and P <0.02 for the first, second, and third assessment, and for the average score, respectively), and this association was independent of early and adult risk factors. In women, the hard-driving component at baseline ( P <0.04) but not later was independently related to thinner carotid IMT. The other components of Type A behavior (impatience-aggression and leadership) were not associated with IMT.
Conclusions- Eagerness-energy component of Type A behavior over different developmental transitions seems to be a robust predictor of IMT in men.
Type A behavior as a predictor of adult carotid artery intima-media thickness (IMT) was examined in a population-based sample of 408 men and 606 women. It was shown that eagerness-energy component of Type A behavior over different developmental transitions seems to be a robust predictor of IMT in men.
【关键词】 atherosclerosis carotid arteries coronary artery disease type A eagernessenergy
Introduction
In the late 1970?s, there was a wide consensus that Type A behavior is an established risk factor of coronary heart disease. 1 Empirical evidence to support the risk factor status was mainly derived from the Western Collaborative Group study, 2,3 and from early findings of the Framingham study. 4 In the 1980?s, belief in the Type A behavior hypothesis vanished because several studies, 5-7 including the later phases of the Framingham study, failed to confirm an association between Type A and CHD. 8 Findings of the Multiple Risk Factor Intervention Trial especially undermined a confidence in an etiologic role of Type A behavior. 9
Studies published in the 1990?s were few in number, and reported both positive 10,11 and negative findings. 12,13 In 1999, Hemingway and Marmot concluded in their clinical review that Type A behavior has a minor etiologic role in coronary heart disease among healthy adults, but no prognostic significance in patients with coronary heart disease. 14
However, several problems and limitations in previous studies may compromise the negative evidence. First, all the negative findings on Type A behavior and atherosclerosis have been derived from samples where almost all subjects were already suffering from coronary artery disease at the time when Type A behavior was assessed. The role of Type A behavior may differ in healthy people from that in subjects with coronary heart disease. Second, development of atherosclerosis is a long-lasting process starting already in childhood. Consequently, examining Type A behavior over different developmental periods since childhood or adolescence would be important. To our knowledge, however, there is no previous study where a potential etiologic significance of Type A behavior had been examined in healthy subjects across different developmental transitions.
Third, prior investigations on atherosclerosis have focused on global Type A behavior and ignored the difference between trait-like (stable personality traits) and state-like (dispositional tendencies elicited by situational variables) components of Type A behavior. Trait-like components would be expected to be more strongly associated with development of atherosclerosis than state-like components.
To reduce these limitations, we examined whether Type A behavior or any of its components assessed in different developmental periods since an early adolescence predict adulthood atherosclerosis after taking into account the impact of established risk factors of coronary heart disease (CHD). Men and women were studied separately, because several previous articles suggest gender-related differences in pathogenic roles of Type A behavior factors. 15-17
Methods
Participants
The Cardiovascular Risk in Young Finns Study is an ongoing follow-up study of coronary heart disease risk factors in Finnish children, adolescents, and young adults. 18 The first cross-sectional study was conducted in 1980 when age cohorts of 3, 6, 9, 12, 15 and 18 years were randomly sampled on the basis of social-security numbers, resulting in a total of 4320 invited participants. From them, 3596 participated in the first study. The first measurement of Type A behavior was performed in 1983, but only for participants at age 12 or older in this follow-up. Measurement of Type A behavior was repeated in subsequent follow-ups in 1986, 1989, and in 2001. The carotid IMT was measured in 2001; participants had then reached age 27 to 39 years. The data used in this study consist of the 1014 participants (408 men and 606 women) with complete information about Type A behavior from 3 assessments, ie, in 1986, 1989, and 2001, and carotid IMT in 2001 ( Figure ). Because of a low number of subjects with Type A assessments, the 1983 follow-up was omitted. Participants have given a written consent, and the study is approved by the local ethics committee.
Flow chart of sample selection.
Type A Behavior
Type A behavior was self-rated with the Hunter-Wolf A-B Rating Scale 19,20 in all follow-ups. The scale consists of 23 items and 4 subscales: (1) impatience-aggression (7 items, eg, "I interrupt others", "I lose my temper easily", I find it difficult to wait", "I like to argue" and "I get angry easily"), (2) leadership (6 items, eg, "I like to tell others what to do", "I am always a leader in activities", "I always like to win"), (3) hard-driving (3 items, eg, "I am hard-driving and competitive", " I take things seriously"), and (4) eagerness-energy (7 items, eg, "I talk fast", " I eat fast", "I walk fast", "I always feel hurried"). The response format for items was a 7 point Likert-scale. We calculated the means of response scores across the scale items with higher values indicating higher level of Type A behavior in each subscale and measurement point. The Cronbach alpha reliabilities of the Type A behavior subscales were acceptable varying between =0.59 (leadership 1986) and =0.76 (eagerness-energy 1989) depending on the subscale and measurement point.
Parental Education and Early Somatic Risk Factors
The education of parents was reported in 1980. Parental education was divided according to the completed school years into 3 categories: low (9 years or under), intermediate, and high (over 12 years). 21 Early somatic risk factors were measured in 1980. Body mass index (BMI) was calculated by dividing participants? weight in kilograms by their squared height in meters. Standardized enzymatic methods were used to obtain high-density lipoprotein cholesterol (HDL-C) and triglycerides. Low-density lipoprotein cholesterol (LDL-C) was calculated according to the Friedewald formula. 22 Blood pressure was measured with a standard mercury sphygmomanometer. 23 For the analysis, early somatic risk factors were standardized by calculating age-specific z-scores.
Adulthood Risk Factors
The participants? own education was reported in 2001, and it was divided into the categories in the same way as the education of their parents (low, intermediate, high). All the adulthood somatic risk factors were assessed as in 1980, except blood pressure which was measured with a random zero sphygmomanometer in 2001. 23 Adulthood glucose concentrations were analyzed enzymatically. 24 The actual scores of adulthood risk factors were used in the analysis with an exception of transformed scores for triglycerides and glucose concentrations.
Smoking habits were acquired by a questionnaire; those smoking on daily basis were defined as smokers. Information on alcohol consumption was acquired by questionnaire asking the drinking habits of the participant (eg, the type and the amount of alcohol that is consumed during a week). The physical activity index (PAI) ( 0.76) was formed by 5 items asking the frequency, intensity, average duration, hours of physical activity, and participation in guided sport (range 5 to 16). 25 High scores on PAI indicate high physical activity.
Carotid IMT
Carotid intima-media thickness was measured with ultrasound mainframes (Sequoia 512 ultrasound; Acuson) with 13.0-MHz linear array transducers. The left common carotid artery was scanned by ultrasound technicians according to a standardized protocol. A minimum of 4 measurements of the common carotid wall were taken to derive mean carotid IMT. 23,26,27 The measurements were done between September 2001 and January 2002. Interobserver cv and intraobserver cv were 5.2% and 4.0%, respectively. 28
Statistical Analyses
The comparisons in baseline characteristics between dropouts and participants and differences in risk factors, type A behavior, and IMT between men and women were studied with t tests. As etiologic factors for men and women may not be the same, all further analyses were stratified by sex. The relationships between early and adulthood risk factors and carotid IMT were examined with age-adjusted linear regression analyses. We averaged the scores of each type A behavior subscale across 1986, 1989, and 2001 and used this average score in the analysis to estimate the effect of long-term type A behavior pattern. To examine the relationship between averaged Type A behavior components and carotid IMT, a series of multivariate linear regression analyses were done. The models were sequentially adjusted for age, early risk factors, and adulthood risk factors. All risk factors were entered into the model as covariates irrespective of their association with IMT, interaction terms between risk factors or type A behavior scores were not tested. As the values of many early risk factors are known to be age-specific, 29 we used age-standardized z-scores of these factors in the analyses. Adulthood triglycerides were log-transformed, and glucose was square root-transformed because of skewed distribution. Finally, to examine whether the association between type A behavior and IMT was robust across all 3 assessment periods, we tested these associations separately with scores from 1986, 1989, and 2001. To reduce the size of tables, this was done only for those type A behavior subscales significantly associated with IMT. All statistical analyses were done with SPSS statistical software, version 13.0.
Results
The present study sample did not differ from the baseline study population with respect to age and sex (all P.05), but the participants of this study had higher LDL-C (3.4. versus 3.3 mmol/L, P <0.05), higher systolic blood pressure (SBP; 114.3 versus 111.8 mm Hg, P <0.001), and lower diastolic blood pressure (DBP; 67.4 versus 69.3 mm Hg, P <0.001) at baseline. In addition, the parents of the participants were more educated (high education 29%) than the parents of the baseline population (high education 23%; P <0.05).
The sample characteristics are shown in Table 1. The mean age was 32.7 in men and 32.6 in women. In childhood and adolescence, men had lower LDL-C ( P <0.05) and triglycerides (<.01) and higher SBP ( P <0.05) than women. In adulthood men had higher BMI, LDL-C, triglyceride, and glucose concentrations, SBP and DBP, and thicker carotid IMT than women ( P <.001). High temporal stability justified the use of average score across the 3 measurement points to indicate Type A behavior components. The 3 year stability for all 4 components varied between r =0.50 and r =0.63 in men, and r =0.54 and r =0.62 in women. The corresponding 15 year stability was from r =0.31 to r =0.50 in men, and from r =0.35 to r =0.48 in women. Men scored higher on the leadership component of the Type A behavior ( P <0.001), but women scored higher on the other components: impatience-aggression ( P <0.001), hard-driving ( P <0.001), and eagerness-energy ( P <0.01).
TABLE 1. Sample Characteristics by Sex
Table 2 shows the associations between early and adulthood risk factors and adult carotid IMT. Greater childhood BMI and SBP were related to thicker carotid IMT in both sexes. The same was true for adulthood risk factors, but in addition, higher diastolic blood pressure was related to thicker carotid IMT in both sexes, and higher concentration of triglycerides was related to thicker carotid IMT in women.
TABLE 2. Standardized ß Coefficients From Age-Adjusted Linear Regression Models for Carotid IMT and Early and Adulthood Risk Factors
Results of multivariate linear regression analyses of carotid IMT and Type A behavior (an average score of 3 assessments) are presented in Table 3. There was a marginal age-adjusted association between global Type A behavior and IMT among men but not among women. Among men, a higher score on eagerness-energy was associated with thicker carotid IMT after controlling for age and early and adulthood risk factors. Among women, higher hard-driving was related to thinner carotid IMT after adjustment for age and early and adulthood risk factors, although an age-adjusted model did not show a significant relationship between this component and carotid IMT. Other components of Type A behavior were not associated with carotid IMT.
TABLE 3. Multiple Linear Regression Analyses for Carotid IMT and Type A Behavior and its Components
Finally, we studied whether the relationships between Type A behavior components and carotid IMT were consistent across the 3 measurement points ( Table 4 ). Among men, higher eagerness-energy scores measured in 1986, 1989, and 2001 were all related to thicker carotid IMT. Among women, higher hard-driving in 1986, but not in 1989 and 2001, was significantly associated with thinner carotid IMT.
TABLE 4. Age-Adjusted Standardized ß Coefficients for Carotid IMT and Eagerness-Energy Among Men and Hard-Driving Among Women by Time of Measurement
Discussion
From the 4 components of Type A behavior, eagerness-energy consistently predicted higher adulthood carotid intima media thickness in men over different developmental transitions during a 15-year follow-up. In addition, hard-driving seemed to be a protective factor in women, although the association manifested only in adolescence and young adulthood, and was not entirely robust to various adjustments. To our knowledge, this is the first prospective study to show a relationship between Type A behavior across developmental periods and carotid atherosclerosis.
Interestingly, Friedman and Rosenman?s first description on Type A person, based on their empirical observations, depicted an eagerness-energy personality, ie, persons with fast and vigorous speech, moving, and gesture stylistics, and with a consistent sense of a great hurry. 30 Other components of the final concept such as aggression, competitiveness, and impatience have been added later on. 31
Eagerness-energy predicted IMT independently of other risk factors. An association between eagerness-energy and traditional CHD risk factors has, however, been previously demonstrated. The Bogalusa study showed an association between eagerness-energy and high levels of serum total cholesterol and triglycerides in children aged 10 to 17 years, 19 and in the current Cardiovascular Risk in Young Finns population, eagerness-energy was correlated with LDL-cholesterol, total cholesterol, and blood pressure in 12-, 15- and 18-year-olds. 15 Furthermore, eagerness-energy predicted increasing levels of components of metabolic syndrome over a 3-year follow-up period in adolescence, especially in girls. 17
The stability over different developmental periods was high for all Type A components, thus the test-retest variance cannot explain why eagerness-energy was the only component that predicted atherosclerosis. Contentually, eagerness-energy component is close to the temperamental dimension of activity, 32 and a person?s activity level has previously been shown to be correlated with his or her Type A behavior. 33 Further, activity level in childhood has been shown to predict an adolescence eagerness-energy, 34 and in women, childhood hyperactivity predicted a carotid intima media thickness over a period of 21 years. 35 Temperaments are shown to be inherited, at least to certain degree, and individual differences in temperaments may reflect differences in metabolic and physiological reactivity. Respectively, a modest but significant heritability has been found for speech and moving stylistics potentially characterizing an activity level, 33 and eagerness-energy has been found to be associated with individual differences in physiological stress reactivity. More specifically, High-S scorers on JAS-S speed and impatience scale (equal to Hunter-Wolf eagerness-energy) took more time than low-S scorers to recover their initial heart rate values after being exposed to a stress. 36 All in all, eagerness-energy might be rooted in stable innate temperaments, especially in temperamental activity.
It is possible that sympathetic nervous system acts as a mediator between Type A and carotid IMT. Oishi et al 37 found that under stress conditions Type A behavior patterns determine short-term responses in physiological variables that are controlled by sympathetic nervous system, such as respiratory rate, skin resistance response, and heart rate variability. On the other hand, we have recently shown that in healthy adults cardiac autonomic task-induced reactivity and recovery are associated with carotid IMT. 38 Thus, there is indirect evidence suggesting that sympathetic nerve activity under stress conditions could play a role in the increased risk for atherosclerosis in Type A individuals.
Among adults, hard-driving has been found to be associated with the occurrence of CHD, 39 whereas in the adolescent subjects of the Cardiovascular Risk in Young Finns study, it has consistently been a protective factor associated with low levels of serum cholesterols, body mass index, and blood pressure 16 as well as a low likelihood of risk behavior accumulation in adolescence and early adulthood. 40 Although the current results on a protective role of hard-driving were in line with previous findings, they were not very robust and the association was dependent on age. Thus, the inverse association between hard-driving and IMT should be taken with a caution.
Here, a higher morbid long-term effect of eagerness-energy was apparent in males but not in females. This gender difference should also be interpreted with caution, because previous findings show that at least in adolescence, eagerness-energy may be risk in girls, too. 15,17 Additional research is needed to confirm gender differences in the association between Type A factors and IMT and to determine how these differences might arise. These studies should take into account the possibility that the same Type A components may play different roles in girls and boys at different ages or developmental periods.
Interpretations of these findings should take into consideration study limitations. As regards the original representativeness of the current study population, reasons for the decline at the baseline (the difference between the invited and participated subjects, see Figure ) are not known, but with respect to the age, gender, and place of residence, no systematic bias existed. 18 The present study sample slightly differed from the baseline study population with respect to childhood LDL-C, systolic and diastolic blood pressures, and parental education, but was representative of the baseline cohort in terms of the other parameters of this study.
Multiple testing was performed for the different components of type A behavior, potentially inflating the chance for false-positive findings. The main analysis comprised 4 tests for each gender, resulting in 2 significant associations. For an alpha level 0.05, 1 in 20 associations would be expected to be significant by chance. In men, the association between eagerness-energy and IMT was expected and robust separate additional analyses across all 3 measurement points. This suggests that chance is an unlikely explanation. In contrast, the inverse association between hard driving and IMT among women was unexpected and not robust across repeated measurements. Thus, we would be cautious in interpreting this finding.
Type A self-ratings were performed in several follow-ups, enabling an emergence of the learning effect. However, it has been shown that repeated personality tests more than 2 years apart are unlikely to be influenced by this effect. 41 The time interval between Type A measures in this study was 3 years at minimum.
Finally, IMT measurements were performed in adulthood only, therefore this study does not provide information on the effects of Type A behavior on the progression of IMT. In addition, we did not have information about participants? Type A behavior before the age of 12 years. Because risk factors before adolescence may contribute to adult IMT, 23,42 it is possible that our study may underestimate the relation between Type A behavior and IMT and that stronger relations would have been revealed if information on Type A behavior at early childhood years had been available. Indeed, the earliest assessments of eagerness-energy was the strongest predictor of adulthood IMT. This may suggest that innate biologically-rooted Type A behavior components could be identified early in life, whereas in adulthood, it might be masked in several ways.
In conclusion, the "core" component of the original Type A behavior predicted a development of carotid atherosclerosis in men. The findings also suggest that stable, probably biologically-rooted Type A behavior components may be more likely to exert their long-term effect on atherosclerosis than the components that have been learned from an environment and are prone to cultural alterations. For understanding the etiologic role of Type A behavior, the life-course approach should be adopted.
Acknowledgments
Sources of Funding
This study has been supported by the Academy of Finland (grants 111056, 209514, 209518 to L.K.-J.; grants 105195 and 117604 to M.K.; and grants 778412 and 210283 to O.R.), the Gyllenberg?s Foundation and the Jansson?s Foundation (to L.K.-J.), the Finnish Foundation of Cardiovascular Research, and Turku University Hospital Research Funds (to J.V. and O.R.), the Finnish Cultural Foundation grant (to T.H.).
Disclosures
None.
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作者单位：Liisa Keltikangas-Järvinen; Taina Hintsa; Mika Kivimäki; Sampsa Puttonen; Markus Juonala; Jorma S.A. Viikari; Olli T. RaitakariFrom the Department of Psychology (L.K.-J., T.H., S.P.), University of Helsinki, Finland; the Department of Epidemiology and Public Health (M.K.), University Colle