Margaret V. Savage

A path model of chronic stress, the metabolic syndrome, and coronary heart disease.

Objective We tested a theoretical stress model cross-sectionally and prospectively that examined whether relationships of chronic stress, psychophysiology, and coronary heart disease (CHD) varied in older adult men (N = 47), older adult women not using hormone replacement therapy (HRT) (N = 64), and older adult women using HRT (N = 41). Method Structural equations examined relationships of CHD with 1) chronic stress (caring for a spouse with Alzheimer’s disease and patient functioning), 2) vulnerability (anger and hostility), 3) social resources (supports), 4) psychological distress (burden, sleep problems, and low uplifts), 5) poor health habits (high-caloric, high-fat diet and limited exercise), and 6) the metabolic syndrome (MS) (blood pressure, obesity, insulin, glucose, and lipids). Results Caregiver men had a greater prevalence of CHD (13/24) than did noncaregiver men (6/23) (p < .05) 27 to 30 months after study entry. This was influenced by pathways from caregiving to distress, distress to the MS, and the MS to CHD. In men, poor health habits predicted the MS 15 to 18 months later, and the MS predicted new CHD cases over 27 to 30 months. In women, no “caregiving-CHD” relationship occurred; however, 15 to 18 months after study entry women not using HRT showed “distress-MS” and “MS-CHD” relationships. In women using HRT, associations did not occur among distress, the MS, and CHD, but poor health habits and the MS were related. Conclusions In older men, pathways occurred from chronic stress to distress to the metabolic syndrome, which in turn predicted CHD. Older women not using HRT showed fewer pathways than men; however, over time, distress, the MS, and CHD were related. No psychophysiological pathways occurred in older women using HRT.

Dim light melatonin onset and circadian temperature during a constant routine in hypersomnic winter depression

The onset of melatonin secretion under dim light conditions (DLMO) and the circadian temperature rhythm during a constant routine were assessed in 6 female controls and 6 female patients with winter depression (seasonal affective disorder, SAD) before and after bright light treatment. After sleep was standardized for 6 days, the subjects were sleep‐deprived and at bedrest for 27 h while core temperature and evening melatonin levels were determined. The DLMO of the SAD patients was phase‐delayed compared with controls (2310 vs 2138); with bright light treatment, the DLMO advanced (2310 to 2135). The minimum of the fitted rectal temperature rhythm was phase‐delayed in the SAD group compared with the controls (0542 vs 0316); with bright light treatment, the minimum advanced (0542 vs 0336).

Circadian temperature and cortisol rhythms during a constant routine are phase-delayed in hypersomnic winter depression

Circadian temperature, cortisol, and thyroid-stimulating hormone (TSH) rhythms during a constant routine were assessed in 6 female controls and 6 female patients with hypersomnic winter depression (seasonal affective disorder, SAD) before and after morning bright light treatment. After sleep was standardized for 6 days, the subjects were sleep-deprived and at bed rest for 27 hours while rectal temperature, cortisol, and TSH levels were assessed. The minimum of the fitted rectal temperature rhythm was phase-delayed in the SAD group compared to the controls 5:42 AM vs. 3:16 AM (p < .005); with bright light treatment, the minimum advanced from 5:42 AM to 3:36 AM (p = .06). The minimum of the cortisol rhythm was phase-delayed in the SAD group compared to the control group, 12:11 AM vs. 10:03 PM (P < .05); with bright light treatment, the minimum advanced from 12:11 AM to 10:38 PM (P = .06) [corrected]. The acrophase of the TSH rhythm was not significantly phase-delayed in SAD subjects compared to control, though the trend appeared to be toward a phase-delay (p = .07). After bright light therapy, the TSH acrophase was not significantly different in the SAD subjects; the trend was a phase-advance (p = .09). Overall, the data suggest that circadian rhythms are phase-delayed relative to sleep in SAD patients and that morning bright light phase-advances those rhythms.

Temperature Regulation in the Neutral Zone

The impressive features of human thermoregulation are the powerful effectors that defend us against hyperthermia-active vasodilation of the blood vessels of the skin, and secretion of sweat. Together, these can keep body temperature within one or two degrees of normal in an exercising person who generates heat at anear-kilowatt rate for hours, for example, in a marathon race.’ Less impressive, in terms of power, is shivering, for cold-exposed humans do not maintain thermal steady states for long through high rates of shivering. Least impressive and least obvious is the subtle modulation of skin blood flow that regulates body temperature over long periods of sedentary or mild activity and “neutral” thermal conditions. Yet it is that unappreciated effector system that accomplishes the thermal balance that we associate with normal body temperature. Clearly, it accomplishes the alterations in steady-state body temperature associated with the diurnal and lunar rhythms and with disturbances in those rhythms. If it means something to state that the “set-point” of body temperature regulation changes with sleep onset, for example, it must be that the parameters of control of skin blood flow in relation to inputs derived from skin and core thermosensors change with sleep onset. Do they? The observed effect might have nothing to do with the thermoregulatory control system per se . For example, lying down alters skin blood flow2” and thus alters the equilibrium core temperature in fixed thermal conditions. Is the apparent set-point shift the consequence of this nonthermal influence? To be able to answer such questions we need better quantitative understanding of the control of skin blood flow and means of measuring the parameters of control.

Are the salutogenic effects of social supports modified by income? A test of an "added value hypothesis".

Older adults (54 men, 113 women; M age = 69.5 years) were examined to test the hypothesis that social supports would be more salutogenic (health promoting) for persons with lower incomes than for persons with higher incomes. Interactions of income and social supports (mean of 3 emotional scales of the Interpersonal Support Evaluation List) at study entry predicted changes 15-18 months later in a cardiovascular composite (linear combination of high-density lipoproteins-mean arterial pressure; p < .05), and natural killer cell activity (p < .05). For both outcomes, emotional supports were salutogenic for persons with lower incomes (< or =

CD4 and CD8 counts are associated with interactions of gender and psychosocial stress.

29,000/year), but not for persons with higher incomes (>

Adenine nucleotide control of coronary blood flow during exercise

29,000/year). In contrast, interactions of the Tangible Support Scale with income did not occur. Persons with lower incomes may derive benefits from social supports that go beyond tangible assistance.

Lymphocyte Proliferation Is Associated with Gender, Caregiving, and Psychosocial Variables in Older Adults

Objective This study examined relationships of gender, psychosocial stress/distress (caregiving, hassles, depressed mood), and the relative percentage and absolute cell counts of CD4 and CD8 cells in two samples of older adults (mean age = 69.4)-spouse caregivers of persons with Alzheimers disease (N = 78) and age- and gender-matched spouses of nondemented controls (N = 72). Methods Counts and percentages of CD4 and CD8 cells and psychosocial variables were assessed twice (Time 1, Time 2) over a 15- to 18-month period. Several covariates were examined in the analyses, including body mass index (BMI), medication use, alcohol use, exercise, and illness history. Results Caregiver men had fewer CD4 cell counts at Times 1 and 2 than did control men (p < .05). At Times 1 and 2, both CD8 cell counts and percentages were positively associated with hassles in men (p < .05), but not in women. Although interactions of hassles and gender were present for CD8 percentages at both times, interactions and main effects were not present for CD4 percentages at either time. When the ratio of CD4 to CD8 levels was analyzed, hassles by gender interactions were present at both Times 1 and 2-hassles were negatively associated with the CD4/CD8 ratio in men (p < .05), but unrelated in women. From Time 1 to Time 2, change analyses showed that increases in hassles scores were associated with decreases in CD4 counts (p < .05), whereas increases in Hamilton Depression Scores were related to increases in both CD8 counts and percentages (p < .05). Conclusion Caregiver status, hassles, and depressed mood had cross-sectional and/or longitudinal associations with CD4 and CD8 counts, but such relationships occurred primarily in men. Moreover, absolute cell counts were more related to psychosocial factors than were percentages.

Body temperature and diurnal type in women with seasonal affective disorder

The adenine nucleotide hypothesis postulates that the ATP released from red blood cells is broken down to ADP and AMP in coronary capillaries and that ATP, ADP, and AMP act on purinergic receptors on the surface of capillary endothelial cells. Purinergic receptor activation initiates a retrograde conducted vasodilator signal to the upstream arteriole that controls coronary blood flow in a negative feedback manner. A previous study (M. Farias 3rd, M. W. Gorman, M. V. Savage, and E. O. Feigl, Am J Physiol Heart Circ Physiol 288: H1586-H1590, 2005) demonstrated that coronary venous plasma ATP concentration increased during exercise and correlated with coronary blood flow. The present experiments test the adenine nucleotide hypothesis by examining the balance between oxygen delivery (via coronary blood flow) and myocardial oxygen consumption during exercise before and after purinergic receptor blockade. Dogs (n = 7) were chronically instrumented with catheters in the aorta and coronary sinus and a flow transducer around the circumflex coronary artery. During control treadmill exercise, myocardial oxygen consumption increased and the balance between oxygen delivery and myocardial oxygen consumption fell as indicated by a declining coronary venous oxygen tension. Blockade of P1 and P2Y(1) purinergic receptors combined with inhibition of nitric oxide synthesis significantly decreased the balance between oxygen delivery and myocardial oxygen consumption compared with control. The results support the hypothesis that ATP and its breakdown products ADP and AMP are part of a negative feedback control mechanism that matches coronary blood flow to myocardial oxygen consumption at rest and during exercise.

Epidural anesthesia and the thermoregulatory responses to hyperthermia - Preliminary observations in volunteer subjects

We examined lymphocyte responses to mitogens [phytohemagglutinin (PHA), concanavalin A, pokeweed] in spouse caregivers of persons with Alzheimers disease (n = 82; mean age = 69.4) and noncaregiver spouses (n = 83) group matched on age and gender. Data were collected at study entry (T1) and 15–18 months later (T2). In men (n = 52), a depressed mood factor was negatively related to all mitogen responses at T1 and PHA at T2. Loneliness was the most important variable in the depressed mood factor. No relationships occurred in women (n = 113). At T2 an anger expression factor (anger-out − anger-control) was negatively related to all mitogen responses in caregivers. Anger-out was the most important variable for anger expression. Depressed mood at T1 predicted residualized changes in PHA at T2 in men. In conclusion, men with higher depressed mood and caregivers with higher anger expression may be at risk for lower proliferation responses.