STRESS MEDICINE, VOL. 10: 255-260 (1994)

INFLUENCE OF STRESS AND BLOOD TYPE ON TOXICITY-PREVENTING ACTIVITY AND

OTHER CARDIAC RISK FACTORS

JOSEPH K. NEUMANN, PhD US Department of Veterans Afairs Medical Center, James H. Quillen College of Medicine, Johnson City, TN, USA

LORETTA Y. ARBOGAST, PhD AND F. AARON DUBBERLEY, BS James H. Quillen College of Medicine, Johnson City, TN, USA

SUMMARY ABO blood type has been shown to be associated with both cardiovascular risk and toxicity-preventing activity (TxPA) stress response in elderly males. Twenty middle-aged, healthy males, 14 blood type A and six blood type 0, were involved in this project. Volunteers completed a battery of psychological assessments, then gave blood and had several psychophysiological measures taken prior to, during and after two stressors. The stressors consisted of mental arithmetic tasks plus audiotapes of combat sounds and a baby crying. The anger-out and hard-driving scores of blood type 0 subjects were significantly higher than the blood type A means. TxPA decreased significantly as a function of stress and some suggestive blood type effects of TxPA were found. Plasma protein, microhematocrit, plasma cortisol, finger temperature, skin conductance, blood pressure and two facial electromyograph (EMG) variables were also significantly affected by stressors but not by the blood type factor. No significant differences of any kind were found for total cholesterol, high-density lipoprotein or pulse variables. The importance of age and other individual subject characteristics was discussed.

KEY WORDS-ABO blood group system, psychological stress, very low density lipoproteins, albumins.

ABO blood type is a known risk factor for several cardiovascular disorders.' For example, myocar- dial infarction (MI) occurs at a higher rate than expected in blood t pe A as compared to type 0 males and females. '?Ph y siological explanations for the varying incidence of MI by blood type have included differential levels of clotting factors, serum cholesterol, blood viscosity and cortisol/ cat echo la mine^.^

Type A behavior pattern has historically been linked to increased cardiovascular di~ease.~ This pattern includes subjective time pressure, cynical hostility and other components that have been explored in the past 20 years. Further, blood type 0 MI patients, the statistically less expected MI blood type, have been found to have higher type A behavior pattern scores than blood type A patient^.^ These and other findings have encour- aged Neumann et to hypothesize that, for adult patients, indices of trait anger, anxiety, depression and type A behavior pattern are in-

Address for correspondence: Joseph K. Neumann, PhD, Psy- chology Service (1 16B2), VA Medical Center, Mountain Home, TN37684, USA. Tel: 615-9261 171, Exl. 7294/7299.

versely correlated with the expected ABO blood type in disorders that are blood type related.

Arbogast et al. have implicated a serum albumin factor, toxicity-preventing activity (TxPA), with increased cardiovascular r i ~ k . ~ * ~ TxPA is an isoelec- tric form of albumin (PI 5.6) which inhibits the in vitro toxicity of very low density lipoproteins (VLDL) to endothelial cells. Clinically, Arbogast et a1.6*8 have reported that TxPA was lower in indi- viduals with angiographically documented coron- ary artery disease (CAD) and have found an atherogenic index incorporating TxPA over 92 per cent and 97 per cent accurate in classifying indivi- duals with CAD.778 TxPA was recently found to be blood type related. Older male subjects (mean age = 62 years) having blood type A had higher initial levels of TxPA as well as quicker stress re- covery levels than blood type 0 volunteers.' The primary purpose of this project was to investigate the stress and blood type (A vs 0) effects on TxPA in a younger male sample.

Blood viscosity has also been related to cardio- vascular disease, stress and ABO blood type." Blood viscosity is higher in blood type A than 0 people and stress seems to increase viscosity. de

CCC 0748-8386/94/04025546 @ 1994 by John Wiley 8t Sons, Ltd.

256 J. K. NEUMANN, L. Y. ARBOGAST A N D F. A. DUBBERLEY

Simone et u1.I’ found that plasma protein and microhematocrit measured by standard procedure were well able to predict blood viscosity. Further, Orr” recommended increased use of skin conduc- tance, finger temperature and facial electromyo- graphs (EMG) to assess stress effects. Orr reported that depressed mood was associated with corruga- tor supercilii EMG while elated mood was corre- lated with zygomaticus EMG changes. The relationships of systolic/diastolic blood pressure, pulse and total cholesterol to cardiovascular func- tion and disease are well e~tablished.’~ TxPA was hypothesized to decrease as a function of stress, with blood type A subjects having higher initial levels and quicker recovery than blood type 0 sub- jects. Exposure to the stressors was hypothesized to increase microhematocrit, plasma protein, pulse, plasma cortisol, both facial EMG measures, skin conductance and total cholesterol and decrease finger temperature. No a priori blood type predic- tions were made for these variables.

METHOD

Subjects This project was approved by institutional

review boards at Mountain Home Veterans Affairs Medical Center and East Tennessee State Univer- sity, Johnson City, Tennessee, USA. Fourteen con- firmed blood type A and six blood type 0 healthy males were recruited from the local community (see Table 1). This is a sample size similar to previous work’ and the maximum that could be recruited given the resources available for this project. All volunteers confirmed verbally and in writing that they had no history of cardiac disease, diabetes, unexplained chest pain, blood or arm skin disease or any hospitalization for alcohol, drug or psychi- atric problems in at least 1 year. Further, all sub- jects stated that they had not taken any prescribed medications in 48 hours or any over-the-counter medications in 24 hours.

Volunteers were generally Caucasian, currently married and high school graduates. None had been involved in research similar to this project. A higher percentage of blood group A were Rh(D)+ but this has no known behavioral hematology risk cor- relate~.~ Health/social/religious rating means of both groups were generally similar. However, blood type A subjects reported significantly more cigarette smoking than type 0 volunteers. Smoking is a well-known risk factor for cardiovascular dis-

Table 1-Subject characteristics

Variable Blood Blood group A* group 0

General Age (years) 40.21 (8.3) 38.17

(14.0) % Caucasian 71 100 ’ ‘YO married 79 61 ‘YO HS grad. 86 100 % Rh(D) + 64 33 %A, subtype. 71 NA

Coffee 2.79 (1.5) 2.00 (0.9) Alcohol 1.57 (1.6) 1.17 (1.2) Cigarettes** 2.29 (1.3) 1 .OO (0.0) Overall stress 3.43 (1 .O) 4.17 (0.4)

Friends 4.79 (1.1) 4.83 (1.3) Church attendance 2.64 (1.6) 2.50 (1.4) Values similar to parents 4.07 (1.9) 3.67 (2.0) Father church attendance 2.00 (0.94) 2.20 (0.84) Mother church attendance**l.54 (0.78) 2.60 (0.55)

* Data, if not percentages, are presented as means (standard deviations).

Health habit rating means

Socialheligious rating means

* * p < 0.02

orders. However, separate smoker vs non-smoker analyses found significant (p < 0.05) differences for only one variable in this study. Smokers had higher microhematocrit levels than non-smokers. The association of ABO blood type with the cigar- ette frequency rating is assumed to be a statistical artifact since two previous studies found no such relati~nship.”~ Interestingly, mothers of group 0 subjects were rated as attending church less fre- quently than mothers of blood group A volunteers. Previous investi ators have found cardiovascular stress response’’ and health” related to parental church involvement but it is not established whether this specific variable independently relates to acute stress response or is a statistical artifact of the multiple tests.

Procedures After signing consent forms, volunteers com-

pleted standardized assessments of anxiety (State- Trait Anxiety Inventory (STAI); Consulting Psy- chologists Press, Palo Alto, CA), depression (Beck Depression Inventory (BDI); The Psychological Corporation, San Antonio, TX), type A behavior pattern (Jenkins Activity Survey (JAS); The Psy- chological Corporation, San Antonio, TX) and

STRESS AND BLOOD TYPE EFFECTS ON TOXICITY-PREVENTING ACTIVITY 257

anger (State-Trait Anger Expression Inventory (STAXI); Psychological Assessment Resources, Inc, Odessa, FL). The STAI and JAS were used by the authors in previous research associating these scales with ABO blood type.3" The Beck and STAXI have been used by others in behavioral medicine and s ecifically linked to cardiovascular functioning.'"''Subjects also completed forms pro- viding general descriptive information prior to a brief break.

A butterfly needle was inserted into a forearm vein and infused with heparin. To eliminate local heparin effects, about 2.5 ml was drawn and dis- carded prior to coilecting each 20 ml sample. Blood was drawn three times before and after each of two 5-minute stressors at 15-minute intervals for a total of nine blood samples. Psychophysiological measures were taken prior to each blood sample as well as 1 minute after each stressor started for a total of 1 1 sample points. Subjects were instructed to relax between blood draws. After the project, each volunteer was asked to rate the subjective stress of the stressors on 13 dimensions." Presen- tation order of stressors was counterbalanced.

The stressor consisted of mental arithmetic sub- traction task while listening to an audiotape of either combat sounds or a baby crying. Both tapes were played at 65 decibels measured at the subject's ear. The combat tape had sounds of guns firing, helicopters, screams, etc, taken from the movie 'Apocalypse Now'. The baby crying tape was a recording of a human infant crying. Each tape had sound segments joined together for a 5-minute con- tinuous tape. Similar tapes have been used in pre- vious stress

Microhematocrit % was determined using a TRIAC centrifuge (Becton Dickinson and Co, Par- sippany, NJ) from blood placed in heparinized tubes. Blood for TxPA assays was placed in tubes with no anticoagulant and allowed to clot for about 2 hours at room temperature. Tubes were centri- fuged at 1000 X g within 3 hours to collect serum and plasma which were frozen at -20°C and stored at -60°C. Plasma protein values (g/dl) were deter- mined prior to freezing using a standard refract- ometer (A0 Scientific Instruments, Keene, NH).

Total serum cholesterol in mg/dl was determined using a commercially available kit (Immuchem Corp, Carson, CA). The procedure for TxPA ana- lyses has been described in detail elsewhere." Briefly, TxPA was assayed by isoelectric focusing of 10 p1 of serum in a IO-ml water-jacketed column at 4°C and was measured in g/dl. Plasma cortisol

(pg/dl) was assayed using an RIA kit from Immu- chem Corp (Carson, CA). High-density lipoprotein (HDL) was measured using a kit from Sigma Che- mical (St Louis, MO).

Skin conductance level (SCL), finger tempera- ture (Temp), electromyograph 1 (EMGl) and elec- tromyograph 2 (EMG2) were determined using the Davicon MEDAC Systemi3 (American Biotec Corp, Ossining, NY) with surface sensors. SCL sen- sors were placed on right indexlring fingers and temperature sensors on the left index finger. The EMGl electrodes were placed on left corrugator supercilii and the EMG2 sensors on the left zygo- maticus major. EMG was measured in microvolts, SCL in microsiemens and temperature in degrees F. Systolic/diastolic blood pressure (mm/Hg) and pulse (BPM) were assessed with a model SD-700A automated blood pressure/pulse monitor (Indus- trial & Biomedical Sensors Corp, Waltham, MA). Psychophysiological measures are available for all subjects. However, we were unable to obtain blood samples for one blood type 0 subject and methodo- logical problems prevented assessing TxPA for two blood type A volunteers. Not all cortisol samples were assayed due to resource limitations.

RESULTS

Psychological assessments

Blood groups A and 0 psychological assessment score means were compared with t-tests for inde- pendent means. No significant (p < 0.05) differ- ences were found for state-trait anxiety or depression assessments. Seven anger subscales were not significantly different between groups. How- ever, the anger-out mean of the blood type 0 sub- jects (1 = 16.00, SD = 3.79) was significantly higher than the blood type A group (1 = 12.43, SD = 2.24); t = 2.64, df = 18, p = 0.02. Three subscales of the Jenkins Activity Survey (JAS) were not different between groups. However, the JAS hard-driving subscale mean of blood type 0 sub- jects (x = 128.33, SD = 25.71) was significantly higher than the blood type A subjects (x = 107.36, SD = 17.93); t = 2.11, df = 18,p = 0.049.

Biochemical variables TxPA decreased significantly as a function of

stressor exposure (F8.120 = 2.27, p < 0.03). Dun-

258 J. K. NEUMANN, L. Y. ARBOGAST AND F. A. DUBBERLEY

Table 2-Biochemical response data* by blood type ~

Sample number TxPA Plasma protein (g/dl) Microhematocrit % Cortisol (pg/dl) A 0 A 0 A 0 A 0

(Needle insertion) 1 0.41 (0.11) 0.41 (0.15) 7.46(0,42) 7.41 (0.39) 48.0(6.3) 46.3(4.5) 13.9(6.5) 16.6(3.9) 2 0.40(0.11) 0.25(0.13) 7.34(0.40) 7.32(0.36) 45.4(6.8) 44.8(4.1) 3 0.38(0.10) 0.37(0.11) 7.32(0.40) 7.27(0.38) 47.2(6.7) 44.3(4.6) 14.7(7.3) 16.6(1.7) (Combat sounds) 4 0.37(0.08) 0.25(0.09) 7.41 (0.42) 7.31 (0.44) 44.9(5.2) 41.8(3.8) 14.4(7.3) 14.7(1.1) 5 0.42(0.09) 0.36(0.08) 7.41 (0.43) 7.31 (0.38) 43.4(4.6) 43.0(3.5) 6 0.40(0.09) 0.34(0.10) 7.40(0.43) 7.32(0.39) 44.9(3.5) 44.0(2.4) llS(7.3) 13.8(4.0) (Baby crying) 7 0.38(0.10) 0.32(0.09) 7.37(0.41) 7.32(0.40) 44.3(3.2) 49.0(9.7) 12.2(7.4) 15.6(3.6) 8 0.38(0.09) 0.30(0.06) 7.38(0.40) 7.29(0.39) 45.2(4.1) M.O(l.9) 9 0.40(0.09) 0.36(0.14) 7.40(0.42) 7.34(0.47) 46.7(5.2) 47.5(7.3) 12.8(8.5) 12.7(3.0)

* Data are given as means (standard deviations). TxPA, toxici ty-preventing activity.

can’s comparisons revealed that sample 1 levels were significantly higher than means of samples 2, 4 and 8 and that the sample 5 mean was significantly higher than the sample 4 mean. The blood type (Fl,15 = 2.53, p c 0.13) and interaction (F8,120 = 1 . 8 5 , ~ c 0.07) terms were suggestive but not statis- tically significant. Blood type A subjects tended to have higher levels of TxPA and be less stress- responsive than blood type 0 subjects. No blood type effect was found in analyses of plasma protein, microhematocrit or cortisol values. However, plasma protein increased as a function of stress (F8,1)6 = 3.58, p < 0.0008) as did microhematocrit (F8.136 = 2.07, p < 0.04) and plasma cortisol (F5,75 = 2.61, p < 0.04) (Table 2). No significant changes were found in total cholesterol or HDL.

Psychophysiological variables No significant blood type effects were found for

any of the psychophysiological variables. The stres- sors did significantly decrease finger temperature (Temp - F10,180 = 4.01, p < O.OOOl), increase skin conductance levels (SCL - Flo,,80 = 2.18, p < 0.02), increase diastolic (Dias - Fl0,180 = 3.23, p c 0.0008) and systolic (Sys - Fl0,180 = 7.00, p C 0.0001) blood pressures, and increase EMGl (F10,180 = 2.40, p < 0.01) and EMG2 (F10,180 = 2.52, p c 0.007) levels (Table 3). Interaction terms for SCL (F10,180 = 2.70, p < 0.004) and EMG2 (F10,180 = 2.29, p < 0.02) reflected that blood type 0 subjects tended to be more stress-responsive than blood type A volunteers. No significant pulse differences were found.

DISCUSSION

The primary focus of this article was to investigate the effects of acute psychological stress” and blood type on toxicity-preventing activity (TxPA). As hypothesized, TxPA decreased in response to stress. Since lower levels of TxPA have been shown in vitro to result in increased endothelial cell damage, psychological stressors may potentiate cardiovascular injury by decreasing TxPA in v i v a However, the effects of blood type (A vs 0) on TxPA are merely suggestive. Blood type A volun- teers tended to have higher TxPA levels and quicker stress recovery but the levels did not reach statisti- cal significance as in previous research with older males.9 Further investigations using larger samples are needed to confirm if the trends seen in this study are significant.

An examination of correlations of age and TxPA levels for the first three samples (prior to the first stressor) suggests that age may correlate inversely more with blood type A than 0 samples. The total group correlations for samples 1, 2 and 3 were -0.25 (p = 0.31), -0.13 (p = 0.59) and -0.35 0, = 0.14), respectively. However, the correlation coefficients for the same three samples were -0.26 (p = 0.37), -0.64, (p < 0.01) and -0.45 (p = 0.10) for blood type A subjects and -0.27 (p = 0.66), 0.49 (p = 0.41) and -0.22 (p = 0.73) for blood type 0 volunteers, respectively. Lower levels of TxPA in older persons may lead to TxPA being more stress-responsive (ie less of a ‘ceiling’ effect) in older than younger persons, especially blood type A individuals. A similar increased response

STRESS AND BLOOD TYPE EFFECTS ON TOXICITY-PREVENTING ACTIVITY 259

Table 3-Psychophysiological response data* by blood type

Sample number SCL @siemens) Temp (“F) Dias (mm/Hg) A 0 A 0 A 0

(Needle insertion) 1 2 3

4 5 6 7

8 9

10 11

(Combat sounds)

(Baby crying)

4.34 (3.5) 2.85 (2.6) 3.04 (2.8)

4.07 (3.4) 4.13 (3.8) 3.34 (3.3) 3.42 (3.5)

4.33 (3.2) 4.04 (2.5) 3.74 (3.5) 2.83 (2.3)

5.32 (3.6) 16.56(31.2) 4.29 (2.6)

4.85 (3.4) 2.77 (1.6) 3.66 (2.0) 2.80 ( 1 -4)

4.20 (2.1) 3.95 (1.7) 3.51 (1.9) 3.11 (1.6)

90.2 (3.3) 93.9 (1.4) 93.3 (1.9)

91.5 (4.2) 90.9 (4.2) 91.9 (4.2) 9 1.9 (4.6)

92.8 (2.0) 92.4 (2.4) 92.4 (3.5) 92.4 (3.7)

89.3 (1.9) 91.9 (1.8) 91.7(1.4)

91.0(3.1) 90.7 (2.7) 91.6 (2.5) 90.6 (2.9)

90.9 (1.5) 90.8 (1.9) 91.3 (1.6) 91.1 (2.6)

80.8(12.1) 80.7(11.3) 79.1 (11.6)

87.1 (12.4) 85.0 (12.2) 82.7 (8.2) 77.1( 16.6)

87.7(11.17) 81.9(13.6) 81.7 (13.1) 83.2 (8.8)

85.7 (12.6) 81.7(12.2) 78.2 (1 1.0)

85.8 (13.9) 82.7 (12.9) 83.3 (14.0) 86.2 (13.6)

92.0 (9.0) 80.3 (1 1.5) 80.0 (1 0.0) 83.0 (14.9)

Sample number SYS (mm/Hg) EMGl @volts) EMG2 @volts)

(Needle insertion) A 0 A 0 A 0

1 132.8 (13.6) 128.8 (16.9) 3.3 (1.0) 3.9 (2.1) 3.4 (2.4) 3.8 (3.3) 2 123.6 (1 1.4) 117.2 (1 1.8) 3.7 (1.9) 4.4 (1.9) 4.1 (7.9) 2.4 (0.7) 3 124.8 (9.1) 119.2(6.6) 2.9 (1.7) 3.3 (1.8) 3.4 (2.8) 2.6 (2.1)

4 136.1(17.5) 125.2 (13.2) 6.2 (5.0) 4.0 (2.1) 4.2 (3.0) 19.4 (35.2) 5 127.7 (14.1) 119.8 (10.2) 6.1 (5.8) 7.6 (6.3) 5.0 (3.0) 31.2 (61.6) 6 122.9(11.9) 118.5(9.5) 3.6(1.7) 3.8 (3.3) 5.8(12.6) 2.1 (0.8) 7 124.3 (13.2) 119.7(8.1) 3.7 (2.0) 5.3 (3.4) 4.9 (5.7) 2.4 (1.3)

8 138.0 (14.3) 125.8 (10.5) 4.5 (3.6) 4.3 (3.3) 4.6 (1.7) 6.6 (5.1) 9 130.4(11.0) 124.7 (14.6) 4.9(4.3) 7.0 (7.9) 5.4 (5.0) 7.1 (4.1)

10 125.7 (9.0) 118.3 (4.4) 3.2(1.7) 3.9 (2.4) 4.0 (3.6) 2.7 (2.2) 11 122.2(12.4) 118.0 (6.1) 3.2(1.5) 4.6 (2.2) 2.5 (1.5) 4.5 (4.1)

* Data are given as means (standard deviations). SCL, skin conductance level; Temp, finger temperature; Dias, diastolic blood pressure; Sys, systolic blood pressure; EMGl, left corrugator supercilii EMG; EMGZ, left zygomaticus major EMG.

(Combat sounds)

(Baby crying)

of catecholamine levels to stress has been shown to occur with increasing It is unclear to what extent catecholamine and other physiological age-related changes may impact on TxPA stress response.

Two findings in this project replicated previous blood type related results. First, blood type 0 sub- jects scored significantly higher than As on the JAS hard-driving subscale, as in a study with MI patients.’ The hard-driving scale has also correlated positively with measures of hostility and anxiety.23 Secondly, blood type 0 s tended to be more stress- responsive than blood type A volunteers, as pre- viously found.’ This increased response to stress was particularly notable in measures of TxPA, SCL

and EMG2. Studies with larger numbers of subjects may better ascertain the validity and extent of these suggestive findings.

The failure to find significant stress-related changes in HDL and total cholesterol may be related to several factors. The mental subtraction and audiotape stressors may not have been suffi- ciently stressful to elicit responses in levels of these compounds. The lipid measures may be too broad and require assessment of subtypes (eg apolipopro- tein A-11). Lastly, the lack of significant differences may relate to the importance of individual differ- ences found in Niaura et al.’sZ4 recent review of lipids in psychological research. Most consistent lipid-related stress changes were found in subject

260 J. K. NEUMANN, L. Y . ARBOGASTAND F. A. DUBBERLEY

groups with an extensive family history of cardio- vascular problems and/or with demonstrated tend- ency to evidence generally high levels of autonomic or neuroendocrine stress reactivity. Further research is needed to better understand the role of personality traits and individual differences such as blood type in stress response. However, TxPA clearly does decrease with stress and this decrease may result in increased cardiovascular health risk.

ACKTJC) WLEDGEMENTS

Funding for this project was provided by the US Department of Veterans Affairs as part of a larger investigation concerning stress responses of veter- ans returning from Operation Desert Storm. The typingklerical contribution of Mrs Pauline Dicker- son and Mrs Betty Lake is gratefully acknowledged as is the laboratory assistance of Drs Bradley Arbo- gast and David Chi and Messrs Russ M. Hellwege and Edward Jones.

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