Lowering Cortisol and CVD Risk in Postmenopausal Women

Transcription

1 Lowering Cortisol and CVD Risk in Postmenopausal Women A Pilot Study Using the Transcendental Meditation Program KENNETH G. WALTON, a JEREMY Z. FIELDS, DEBRA K. LEVITSKY, DWIGHT A. HARRIS, NIRMAL D. PUGH, b AND ROBERT H. SCHNEIDER a Institute for Natural Medicine and Prevention, College of Maharishi Consciousness- Based Health Care, Maharishi University of Management, Fairfield, Iowa 52557, USA b National Center for Natural Products Research, School of Pharmacy, University of Mississippi, Oxford, Mississippi 38655, USA ABSTRACT: Unlike younger women, the risk of cardiovascular disease in older women matches or exceeds that of men. Excessive cortisol may play a role in this increased risk. Here we explore the possibility that the Transcendental Meditation (TM) program may reduce the cortisol response to a metabolic stressor as a way of reducing disease risk in older women. Data from 16 women who were long-term practitioners of transcendental meditation (mean = 23 y) were compared with data from 14 control women matched for age (mean = 75 y, range = y). Data on demographics, disease symptoms, and psychological variables were collected, and cortisol response to a metabolic stressor (75 g of glucose, orally) was examined in saliva and urine. Pre-glucose levels of salivary cortisol were identical for the two groups. Post-glucose cortisol rose faster in the controls and was significantly higher than that in the TM women (P < ). Urinary excretion of cortisol during this period was 3 times higher in controls than in the TM women (2.4 ± 0.17 and 0.83 ± 0.10 µg/h, respectively; P = ). In addition, the number of months practicing transcendental meditation was inversely correlated with CVD risk factors. Lower cortisol response to metabolic challenge may reflect improved endocrine regulation relevant to the disease-preventing effects of transcendental meditation in older women. KEYWORDS: cortisol; cardiovascular disease; menopause; meditation; metabolic syndrome INTRODUCTION Cardiovascular disease (CVD) is primarily a disease of the elderly. In the United States, by age 65, CVD is the major cause of death in women as it is in men. 1,2 In Address for correspondence: Kenneth G. Walton, PhD, 1000 N 4th St., FM 1005, Fairfield, IA Voice: , ext. 111; fax: kwalton@mvm.edu Ann. N.Y. Acad. Sci. 1032: (2004) New York Academy of Sciences. doi: /annals

2 212 ANNALS NEW YORK ACADEMY OF SCIENCES women, the large increase in CVD risk that occurs during and after menopause is not entirely due to declines of sex hormones, because hormone replacement therapy does not remove CVD risk; in some cases it only adds to it. 3,4 A more likely candidate for increased postmenopausal risk for CVD and CVDrelated mortality is increased stress or increased stress responsiveness Increased stress responsiveness after menopause has been observed in both cardiovascular and neuroendocrine systems. 9,11 13 Such stress-related alterations appear to be relevant to the observed differences in hemodynamics, left ventricular structure, and nighttime blood pressure dipping between pre- and postmenopausal women. 14,15 Evidence for a deleterious influence of menopause on fat metabolism also exists Increased visceral fat is particularly strongly associated with chronic stress, CVD, and risk factors for CVD, including the cluster of risk factors identified as the metabolic syndrome, 19,20 including three or more of the following: hyperinsulinemia, hyperglycemia, abdominal obesity, hypertension, and hyperlipidemia. Excessive levels of the stress-induced hormone cortisol may play a role in this increased susceptibility to CVD in older women, and some natural medicine approaches may prevent or reverse this chronic increase of cortisol (see Ref. 21 for a review). To explore the possibility that such approaches can reduce cortisol response to stress, we cross-sectionally examined the long-term effects of the Transcendental Meditation program, a component of the traditional system of health care known as Maharishi Consciousness-Based Health Care, previously reported to reduce stress, cortisol, and CVD risk. 21 METHODS Data from 16 women (mean age 75 y) who had practiced the Transcendental Meditation program long-term (mean 23 y) were compared with data from 14 control women, matched for age, who had practiced no systematic program for stress reduction. For comparison, male subjects of the same age (10 Transcendental Meditation subjects and 11 controls) were also studied. Data on demographics, disease symptoms, and psychological variables were collected, and cortisol response to a metabolic stressor (75 g of glucose administered orally) was examined in saliva and urine. Cortisol was analyzed by radioimmunoassay (Diagnostic Products Corp., Los Angeles, CA) as previously published, 22 with a coefficient of variation of 3.6%. Other measures used standardized test instruments and procedures. The testing procedure was as follows. Subjects began arriving at 10:30 AM and were asked to urinate in the toilet to empty their bladders. They recorded this time as the starting time for urine collections. Between this time and the end of testing (3 PM), all urine generated was collected in a single bottle for each subject, with the last timed urination occurring as close to 3 PM as possible. At 11 AM, all subjects began salivary collections and filled out questionnaires. Urine and saliva samples were stored frozen until assay. At 12 noon, subjects consumed 75 g of glucose in water flavored with the juice of lemon or lime. Blood pressure measurements were conducted throughout the period, with each subject being measured three times at least 15 min apart.

3 WALTON et al.: CORTISOL AND CVD RISK AFTER MENOPAUSE 213 FIGURE 1. Response of salivary cortisol to oral glucose in postmenopausal women. The statistical comparison is for those points after consumption of glucose, that is, from 12:15 onward, covarying for the 12 noon data point. RESULTS The control and Transcendental Meditation groups of women were not significantly different on demographic and lifestyle variables (i.e., age, education, income, exercise level, smoking, alcohol consumption, and weight) or family history of disease (i.e., CVD, cancer, and allergies). However, FIGURE 1 shows that the response of salivary cortisol to the glucose bolus administered at 12 noon was significantly different for the two groups of women (P =.0001, repeated measures ANOVA), with the control group rising 7.5 times faster than the Transcendental Meditation group between the 12:15 and 12:30 PM time points. By contrast, for the men, the control group responded only weakly to glucose and was significantly less responsive than the Transcendental Meditation group (not shown). In the Transcendental Meditation subjects, the cortisol response to glucose was significant for the men and women s groups and was of similar magnitude and duration in men and women. In women, the group differences in urinary excretion of cortisol over the 4-h period were parallel to those in salivary cortisol. Control women had threefold greater cortisol excretion than did the Transcendental Meditation women (2.4 ± 0.17 and 0.83 ± 0.10 µg/h, respectively; P = ). The initial rate of glucose-induced rise in salivary cortisol, as shown by the difference between the 12:15 and 12:30 time points, correlated highly with urinary cortisol excretion across all women (Pearson correlation coefficient: r =.82; n = 29, P < ). On the other hand, cortisol excretion rates in men appeared not to correlate with the relative increases in salivary cortisol. Control men had 1.5-fold greater urinary cortisol excretion than did Transcendental Meditation men (1.89 ±.30 vs ±.14 µg/h, respectively; P =.06) despite the higher salivary cortisol response to glucose in the Transcendental Meditation men than the control men. Two other correlations were noteworthy. In the Transcendental Meditation group of women, the number of months practicing the technique correlated negatively with cortisol excretion (r =.63, P =.015). The number of months practicing the technique also correlated negatively with the number and severity of symptoms of heart disease, as determined by a nine-item questionnaire (r =.91; P = ).

4 214 ANNALS NEW YORK ACADEMY OF SCIENCES DISCUSSION These findings suggest that long-term practice of the Transcendental Meditation program reduces the response of the hypothalamic-pituitary-adrenocortical (HPA) axis to a bolus of glucose in postmenopausal women. Studies in younger subjects, both men and women, also support a normalizing effect of this program on the HPA axis The present findings are the first to suggest that a meditation technique can reduce the effects of a metabolic stressor on the HPA axis. Because elevated cortisol may be a causal factor in producing the metabolic syndrome, the apparent ability of the Transcendental Meditation program to reduce cortisol response to a metabolic stressor may play a role in the preventive effects of this program on CVD and coronary disease. 25 REFERENCES 1. WENGER, N.K Coronary heart disease: an older woman s major health risk. Brit. Med. J. 315: LEWIS, S.J Cardiovascular disease in postmenopausal women: myths and reality. Am. J. Cardiol. 89: 5E 10E. 3. WELTY, F.K Women and cardiovascular risk. Am. J. Cardiol. 88: 48J 52J. 4. NELSON, H.D., L.L. HUMPHREY, P. NYGREN, et al Postmenopausal hormone replacement therapy: scientific review. JAMA 288: SAAB, P.G., K.A. MATTHEWS, C.M. STONEY & R.H. MCDONALD Premenopausal and postmenopausal women differ in their cardiovascular and neuroendocrine responses to behavioral stressors. Psychophysiology 26: LINDHEIM, S.R., R.S. LEGRO, L. BERNSTEIN, et al Behavioral stress responses in premenopausal and postmenopausal women and the effects of estrogen. Am. J. Obstet. Gynecol. 167: OWENS, J.F., C.M. STONEY & K.A. MATTHEWS Menopausal status influences ambulatory blood pressure levels and blood pressure changes during mental stress. Circulation. 88: MATTHEWS, K.A., J.F. OWENS, L.H. KULLER, et al Stress-induced pulse pressure change predicts women's carotid atherosclerosis. Stroke 29: BAIREY MERZ, C.N., W. KOP, D.S. KRANTZ, et al Cardiovascular stress response and coronary artery disease: evidence of an adverse postmenopausal effect in women. Am. Heart J. 135: CHAPUT, L.A., S.H. ADAMS, J.A. SIMON, et al Hostility predicts recurrent events among postmenopausal women with coronary heart disease. Am. J. Epidemiol. 156: SAAB, P.G., K.A. MATTHEWS, C.M. STONEY, et al Premenopausal and postmenopausal women differ in their cardiovascular and neuroendocrine responses to behavioral stressors. Psychophysiology 26: LINDHEIM, S.R., R.S. LEGRO, L. BERNSTEIN, et al Behavioral stress responses in premenopausal and postmenopausal women and the effects of estrogen. Am. J. Obstet. Gynecol. 167: OWENS, J.F., C.M. STONEY & K.A. MATTHEWS Menopausal status influences ambulatory blood pressure levels and blood pressure changes during mental stress. Circulation 88: HINDERLITER, A.L., A. SHERWOOD, J.A. BLUMENTHAL, et al Changes in hemodynamics and left ventricular structure after menopause. Am. J. Cardiol. 89: SHERWOOD, A., R. THURSTON, P. STEFFEN, et al Blunted nighttime blood pressure dipping in postmenopausal women. Am. J. Hypertens. 14: TORNG, P.L., T.C. SU, F.C. SUNG, et al Effects of menopause on intraindividual changes in serum lipids, blood pressure, and body weight--the Chin-Shan Community Cardiovascular Cohort study. Atherosclerosis 161:

5 WALTON et al.: CORTISOL AND CVD RISK AFTER MENOPAUSE MATTHEWS, K.A., R.R. WING, L.H. KULLER, et al Influence of the perimenopause on cardiovascular risk factors and symptoms of middle-aged healthy women. Arch. Intern. Med. 154: LINDQUIST, P., C. BENGTSSON, L. LISSNER, et al Cholesterol and triglyceride concentration as risk factors for myocardial infarction and death in women, with special reference to influence of age. J. Intern. Med. 251: HERNANDEZ-ONO, A., G. MONTER-CARREOLA, J. ZAMORA-GONZALEZ, et al Association of visceral fat with coronary risk factors in a population-based sample of postmenopausal women. Int. J. Obes. Relat. Metab. Disord. 26: VAN PELT, R.E., E.M. EVANS, K.B. SCHECHTMAN, et al Contributions of total and regional fat mass to risk for cardiovascular disease in older women. Am. J. Physiol. Endocrinol. Metab. 282: E1023 E WALTON, K.G., R.H. SCHNEIDER, S.I. NIDICH, et al Psychosocial stress and cardiovascular disease 2: Effectiveness of the Transcendental Meditation program in treatment and prevention. Behav. Med. 28: WALTON, K.G., N, PUGH, P, GELDERLOOS, et al Stress reduction and preventing hypertension: preliminary support for a psychoneuroendocrine mechanism. J. Alternative and Complementary Med. 1: JEVNING, R., A.F. WILSON & W.R. SMITH Adrenocortical activity during meditation. Horm. Behav. 10: MACLEAN, C., K. WALTON, S. WENNEBERG, et al Effects of the Transcendental Meditation program on adaptive mechanisms: changes in hormone levels and responses to stress after 4 months of practice. Psychoneuroendrocrinology 22: PUTTONEN, S., L. KELTIKANGAS-JARVINEN, N. RAVAJA, et al Affects and autonomic cardiac reactivity during experimentally induced stress as relaeed to precursors of insulin resistance syndrome. Int. J. Behav. Med. 10: