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Biomedical subjects

Matthew F Muldoon

Publications and source records attributed to Matthew F Muldoon.

33 records · Page 2Linked to original sources
PubMed2004

Psychological and cognitive function: predictors of adherence with cholesterol lowering treatment.

BACKGROUND: Failure to adhere to medication regimes is a significant problem in clinical and research settings yet reliable, consistent identification of key psychosocial predictors remains elusive. Studies of mood and personality related to adherence show mixed results-compliance and objectively measured cognitive function are intuitively related but empirical support is lacking. PURPOSE: This study is a secondary analysis to examine the relations between adherence with a medication regime for lowering serum cholesterol and several domains of psychological and cognitive functioning. METHODS: Participants in the initial study completed a measure of personality and a battery of neuropsychological measures at baseline; anxiety and depression were measured at baseline and at 4-week intervals. Medication adherence was tracked with electronic cap monitors for 24 weeks. RESULTS: Only 23% of the sample was fully adherent to medication regimes at least 80% of the time over the 6-month study period. Conscientiousness, according to the Five Factor Theory of Personality, and estimated IQ remained robust predictors of adherence in hierarchical regression analyses. Depression and anxiety, mental flexibility, and visuospatial-constructional ability were less robust but statistically significant (p <.05) correlates of adherence. CONCLUSIONS: Although results of this analysis explain only a portion of the variance in adherence, they demonstrate the importance of trait psychological and cognitive factors in adherence research.

Adult↗
PubMed2004

Low central nervous system serotonergic responsivity is associated with the metabolic syndrome and physical inactivity.

The metabolic syndrome, recognized by the co-occurrence of general or abdominal obesity, hypertension, dyslipidemia, insulin resistance, and dysglycemia, appears to involve disturbances in metabolism, autonomic function, and health-related behaviors. However, physiological processes linking the components of the metabolic syndrome remain obscure. The current study examined associations of central nervous system serotonergic function with each metabolic syndrome risk variable, the metabolic syndrome, and physical activity. The subjects were 270 adult volunteers who participated in a study of cardiovascular disease risk factors and neurobehavioral functioning. Central serotonergic responsivity was indexed as the prolactin (PRL) response evoked by the serotonin-releasing agent, fenfluramine. Across the sample, low PRL response was associated with greater body mass index, higher concentrations of triglycerides, glucose, and insulin, higher systolic and diastolic blood pressure, greater insulin resistance, and less physical activity (P < 0.03-0.001). There also existed an inverse linear relationship between PRL response and the number of metabolic syndrome risk factors individuals possessed (P for trend = 0.002). Finally, a 1 SD decline in PRL response was associated with an odds ratio for the metabolic syndrome of 2.05 (95% confidence interval, 1.10-3.83; P = 0.002) and 5.70 (95% confidence interval, 1.69-19.25; P = 0.005), according to the definitions of the National Cholesterol Education Program and the World Health Organization, respectively. These findings reveal a heretofore unrecognized association between reduced central serotonergic responsivity and the metabolic syndrome.

Adult↗
PubMed2003

Blunted fenfluramine-evoked prolactin secretion in hypertensive rats.

Plasma prolactin (PRL) levels after acute administration of fenfluramine (FEN) have been used as a probe of brain serotonin activity. FEN-evoked increases in PRL levels inversely correlate with arterial blood pressure (ABP) in humans (Muldoon et al. Hypertension. 1998;32:972-975), thereby suggesting that brain serotonin activity may be reduced in hypertension. The present study sought to determine whether the relation between FEN-evoked PRL levels and ABP was present in two rat models of hypertension. Experiments were performed in awake male rats that were instrumented with femoral arterial and venous catheters 2 days before experiments. FEN (3.0 mg/kg IV) significantly increased plasma PRL levels in both spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY); however, FEN-evoked PRL levels were significantly lower in SHR compared with WKY, though baseline levels were similar between strains. Similar results were obtained in rats with chronic hypertension produced by figure-8 renal wrap plus contralateral nephrectomy. In contrast, the increase in PRL levels evoked by the serotonin receptor agonist m-CPP or the dopamine receptor antagonist eticlopride did not differ between SHR and WKY, indicating that PRL secretion is not generally blunted in chronic hypertensive rats. Furthermore, FEN-evoked PRL levels were not attenuated in rats made acutely hypertensive by an infusion of the alpha-adrenergic agonist phenylephrine. Thus, the present findings are consistent with the human data and suggest that chronic hypertension is associated with a presynaptic alteration in brain serotonin function.

Acute Disease↗
PubMed2002

Psychosocial demands and ambulatory blood pressure: a field assessment approach.

Ambulatory blood pressure (ABP) has been shown to have independent prognostic value, over and beyond the effects of clinic blood pressure (CBP) measures. We have examined the role of psychosocial demands in understanding ABP, using an electronic diary to measure ongoing experience in the field at the time of each blood pressure reading (ecological momentary assessment). In our previous work, several psychosocial factors were shown to be associated, within-person, with acute fluctuations in ABP in a healthy adult sample. Here, we replicate these findings in a new sample, and we also examine associations of the same variables with mean ABP (between-person) over a 6-day period. Five measures assumed to be markers of psychosocial demands (negative affect, arousal, task demand, decisional control, and social conflict) were shown here to be independently associated with ABP fluctuations during daily life, after adjustment for posture, activity, and substance use. Two of these, measures of task demand and decisional control, were also associated with mean ambulatory systolic blood pressure (SBP), and these latter associations persisted after controlling for CBP. These results support the possibility that psychosocial factors may account for some of the unique predictive value associated with ABP, and they support the value of these field assessment methods.

Aged↗
PubMed2002

Central nervous system serotonergic responsivity and aggressive disposition in men.

To determine whether normative variability in aggressive behavior correlates negatively with central nervous system (CNS) serotonergic function among men, plasma prolactin (PRL) responses to a standard fenfluramine challenge (administered to assess central serotonergic responsivity) were examined in relation to interview-assessed aggression histories among 118 adult males derived from a nonpatient, community sample. Fenfluramine-induced, peak PRL rises were smaller in subjects whose 'aggression' scores fell above the sample median, compared to their less aggressive counterparts (P<.002). Across subjects, participants' peak PRL responses likewise covaried inversely with aggression history (r(s)=-.32, P<.0005). Additional analyses were conducted on data of 58 subjects who had also been genotyped for a functional polymorphism in the promoter region of the X chromosomal, monoamine oxidase-A (MAO-A) gene. The four variants of this repeat polymorphism were grouped for analysis (alleles '1+4' vs. '2+3') based on prior report of enhanced transcriptional efficiency in MAO-A promoter constructs containing alleles 2 and 3 (repeats of intermediate length). Men in the 2/3 allele group had significantly higher aggression scores (P<.05) and smaller peak PRL responses to fenfluramine (P<.009) than men in the 1/4 allele group. When adjusted by analysis of covariance for concomitant variability in subjects' PRL responses, aggressive disposition no longer varied significantly by genotype. This finding suggests that association of the MAO-A promoter polymorphism with this behavioral phenotype may be mediated, in part, by allele-specific variation in central serotonergic responsivity.

Adult↗
PubMed2002

Retest reliability of prolactin response to dl-fenfluramine challenge in adults.

Neuropharmacologic probes to assess central nervous system (CNS) serotonergic responsivity (e.g., dl-fenfluramine) stimulate serotonergic neurotransmission, thereby causing proportional release of pituitary-derived hormones into the circulation. Individual differences in these hormonal responses are thus thought to reflect dimensional variability in central serotonergic activity, which may, in turn, underlie variation in serotonin-related traits of personality (e.g., impulsivity, behavioral inhibition, harm avoidance). However, the long-term temporal stability of neuropharmacologic indices of CNS serotonergic responsivity has not previously been tested in nonpsychiatric patients. dl-Fenfluramine was administered here to 57 adults, aged 24-60 years, on two occasions 6 months apart, to examine the retest reliability of fenfluramine-induced prolactin [PRL] response to fenfluramine. Baseline PRL concentration (i.e., before administration of fenfluramine) was highly stable over the 6 months (r = 0.88). Variability in serotonergic responsivity, adjusted for baseline PRL concentration, age, sex, and drug concentration during the challenge, was moderately reproducible (r = 0.50 for peak DeltaPRL and 0.57 for PRL "area under the curve," p <.0001). These findings are consistent with speculation that variability in indices of central serotonergic function reflects a temporally stable dimension of individual differences.

Adult↗
PubMed2002

Greater intima-media thickness in the carotid bulb is associated with reduced baroreflex sensitivity.

The aim of this study was to evaluate the association between resting baroreflex sensitivity (BRS) and carotid intima-media thickness (IMT), a putative marker of subclinical atherosclerosis. Participants were 64 men and 18 women (median age, 57 years; range, 40 to 70 years), who did not have a previous history of coronary artery disease or treatment for hypertension. Resting BRS was measured during a 9-min baseline period using the noninvasive sequence technique; carotid IMT was subsequently determined using ultrasonography. Hierarchical multiple regression analyses showed that greater IMT in the carotid bulb (an area with a high density of baroreceptors) was associated with reduced BRS. These findings remained after adjusting BRS for resting mean arterial pressure, age, body mass index, gender, and smoking history, R2 = 0.06, P = .03. In contrast, IMT in the common and internal carotid regions (areas with presumably lower baroreceptor densities) did not account for a significant proportion of the variance in BRS. These results suggest that subclinical atherosclerosis, specifically in a region with high baroreceptor density, is associated with a reduced sensitivity of the baroreflex.

Adult↗
PubMed2002

The incremental value of ambulatory blood pressure persists after controlling for methodological confounds: associations with carotid atherosclerosis in a healthy sample.

BACKGROUND: Ambulatory blood pressure assessments have been shown to be associated with subclinical and clinical endpoints even after controlling for the effects of clinic blood pressure. OBJECTIVE: To examine the incremental validity of ambulatory over clinic blood pressures using equivalent time periods, equivalent numbers of observations, and comparable measurement instruments across both settings. DESIGN AND METHODS: In this cross-sectional study of 216 healthy, community volunteers (ages 50-70 years), we compared three types of assessment in terms of their association with carotid artery atherosclerosis: manual clinic blood pressure (two readings, 10 min interval), automated clinic blood pressure (four readings, 2.5 h interval), and automated ambulatory blood pressure (four readings, 2.5 h interval) using the same type of automated device for the latter two conditions. These measurements were obtained during the morning hours on three separate occasions. Carotid intima-medial thickness and plaque were assessed, by ultrasound, as markers of atherosclerosis. RESULTS: Greater ambulatory systolic and diastolic blood pressure were associated with increased intima-medial thickness and an increased prevalence of plaque (odds ratios > 3.0), even after statistical adjustment for clinic blood pressure assessments and demographic covariates. CONCLUSIONS: We conclude that the independent utility of ambulatory over clinic blood pressure cannot be attributed to methodological issues that have traditionally confounded these comparisons. These findings highlight the potential importance of behavioral and lifestyle factors in contributing to the incremental value of ambulatory blood pressure.

Aged↗
PubMed2002

Effects of six anti-hypertensive medications on cognitive performance.

OBJECTIVE: To describe and compare the effects of six different antihypertensive medications on cognitive performance. DESIGN: Prospective, randomized, and double-blind with treatment cross-over. SETTING: University hypertension clinic and neuropsychology laboratory. PARTICIPANTS: Ninety-eight Caucasian men between 25 and 55 years of age with mild-to-moderate essential hypertension (88 of whom completed the study), and 32 normotensive men with similar socio-demographic characteristics. INTERVENTIONS: Six-week treatment periods with atenolol, metoprolol, hydrochlorothiazide, methyldopa, enalapril and verapamil, and 2-week placebo baseline and wash-out periods. MAIN OUTCOME MEASURES: In-depth neuropsychological assessments and several mood questionnaires were completed during placebo (baseline) periods and active treatment periods. Practice effects due to repeated neuropsychological testing were estimated from data collected concurrently in the normotensive participants. RESULTS: The antihypertensive treatments lowered blood pressure comparably and did not affect mood or anxiety. Small treatment effects were noted in four of seven domains of cognitive performance. Irrespective of medication type, treatment reduced the simple motor speed (P < 0.001), and slowed completion of two tests measuring perceptuo-motor speed and mental flexibility (P </= 0.05). Manual dexterity declined somewhat with metoprolol and methyldopa (P = 0.01). In contrast, all antihypertensive agents favorably affected performance on several tests that require working memory (P < 0.01). Performance on other tests assessing grip strength, learning and memory, attention and executive function was not affected. CONCLUSION: Short-term treatment with standard antihypertensive medications was associated with some small decrements in psychomotor performance and small improvements in working memory, without notable drug-class differences. Long-term effects await further study.

Adult↗
PubMed2002

Is cardiovascular reactivity associated with atherosclerosis among hypertensives?

Exaggerated cardiovascular reactivity to behavioral challenges among otherwise healthy individuals has been associated with carotid atherosclerosis. We evaluated whether a similar relationship exists among hypertensives, who are at a heightened atherosclerotic risk. Untreated, hypertensive men (n=251; age range, 40 to 70 years; 197 white, 54 black) completed a standardized battery of behavioral challenges while their blood pressure responses to the battery were measured. Mean and maximum carotid intima-media thickness and the occurrence of carotid plaques were subsequently determined using B-mode ultrasonography. Although greater systolic and diastolic responses to the battery were associated with greater mean and maximum intima-media thickness in univariate analyses (P<0.01), only diastolic reactivity showed a unique association with mean and maximum carotid intima-media thickness after multivariate adjustment for age, race, socioeconomic status, smoking and alcohol use, body mass index, lipid profile, glucose and insulin concentrations, and resting blood pressure (P<0.05). Carotid plaque occurrence was associated with greater systolic reactivity (P=0.05) and was marginally associated with greater diastolic reactivity (P=0.07) in univariate analyses, but neither systolic nor diastolic reactivity was uniquely associated with the presence of carotid plaques after multivariate risk-factor adjustment. Among hypertensives, exaggerated behaviorally evoked cardiovascular reactivity appears to be uniquely associated with greater carotid intima-media thickness but not with carotid plaque occurrence.

Adult↗
PubMedDate not supplied

Cognitive performance is associated with macronutrient intake in healthy young and middle-aged adults.

PRIMARY OBJECTIVE: The objective was to examine whether dietary intakes of macronutrients are associated with neuropsychological performance. RESEARCH DESIGN AND METHOD: Study participants were 3960 adults aged 20-59 years, who completed three neuropsychological tests and a 24-hour dietary recall as a part of the Third National Health and Nutrition Examination Survey, 1988-1994. Poor performance was defined as the test score below gender-specific 15th percentile. MAIN OUTCOMES AND RESULTS: While holding the energy percentages from different macronutrients, additional 100 kcal intake of energy was associated with a reduced odds of poor performance on serial digital learning test (OR = 0.98, 95% CI = 0.96, 0.99) and symbol digital substitution test (OR = 0.97, 95% CI = 0.96, 0.99). Compared with equivalent energy from carbohydrates, each 5% of energy from poly-unsaturated fatty acids (PUFA) or total fat was associated with a reduced OR of poor performance on simple reaction time test (PUFA: OR = 0.77, 95% CI = 0.63-0.95 and total fat: OR = 0.93, 95% CI = 0.87, 0.99). Poor global cognition was associated with an additional intake of 100 mg cholesterol (OR = 1.14, 95% CI = 1.05, 1.23). These associations were more salient in men. CONCLUSION: Habitual intake of macronutrients is weakly but significantly associated with cognitive functioning. These relationships are more evident in men.

Adult↗
PubMedDate not supplied

Effects of hemoconcentration and sympathetic activation on serum lipid responses to brief mental stress.

OBJECTIVE: Previous studies suggest that hemoconcentration may be one mechanism by which acute psychological stress causes elevations of serum total cholesterol and its subfractions. Alternatively, such elevations may result from sympathetically mediated changes in lipid metabolism. This study evaluated these two hypotheses by manipulation of sympathetically mediated responses to stress using a nonselective adrenoceptor antagonist, labetalol. METHOD: In a 2 x 2 factorial design, 52 healthy male participants were randomly assigned to a stress or no-stress condition and, within each condition, were administered either labetalol or saline. Participants assigned to stress completed three cognitive and evaluative tasks lasting a total of 18 minutes. Indices of hemoconcentration (hematocrit and hemoglobin), heart rate, blood pressure, and serum lipids (total, high-density lipoprotein (HDL), low-density lipoprotein (LDL), free fatty acids, and triglycerides) were assessed at preinfusion and infusion baselines and after mental stress (or rest). RESULTS: Labetalol reduced sympathetic activation, as shown by a substantial reduction in heart rate elevation during stress, but did not alter changes in blood pressure or in hemoconcentration, as indicated by equivalent increases in hematocrit and hemoglobin in the two stressed groups. Labetalol blocked stress-induced increases in free fatty acid concentrations and lowered triglyceride levels but did not influence rises in total, HDL, or LDL cholesterol among stressed subjects. However, arithmetic correction for hemoconcentration eliminated the increases in total, HDL, and LDL cholesterol. CONCLUSIONS: These findings suggest that elevations in total cholesterol and its HDL and LDL subfractions during acute stress are caused by accompanying hemoconcentration, whereas concomitant rises in free fatty acids and triglycerides result from the direct metabolic effects of sympathetic activation.

Adolescent↗
PubMedDate not supplied

Anger-related personality traits and carotid artery atherosclerosis in untreated hypertensive men.

OBJECTIVE: To determine whether anger-related personality traits are associated with carotid artery atherosclerosis in untreated hypertensive patients. METHODS: Study participants were 237 men with elevated blood pressure (systolic 140-180 mm Hg and/or diastolic 90-110 mm Hg) but untreated for hypertension. Average age was 56 years; 80% of subjects were white. Eighty-six percent had no history of antihypertensive treatment, and the remainder reported median lifetime treatment exposure of 4 months. Subjects were administered the Spielberger State-Trait Anger Expression Inventory, which measures tendencies to experience anger (Trait Anger) and modes of anger expression (Anger-In, Anger-Out, Anger-Control). Mean and maximum intima-medial thickness (IMT) and plaque occurrence in the extracranial carotid arteries were measured by B-mode ultrasonography. RESULTS: Trait Anger was marginally (p =.065) related to mean and significantly (p <.05) related to maximum IMT, independent of standard risk factors (age, race, body mass index, education, smoking, fasting glucose, total:high-density lipoprotein cholesterol ratio). A component of Trait Anger, Angry Temperament, similarly predicted mean (p =.062) and maximum IMT (p <.05) and plaque occurrence (p <.05). Anger-Out predicted both mean and maximum IMT (p values <.01). CONCLUSIONS: An antagonistic disposition (Trait Anger), particularly a tendency to experience anger on minimal provocation (Angry Temperament) and a propensity to express anger outwardly (Anger-Out), are associated with heightened carotid atherosclerosis. These findings suggest that recently reported prospective associations between these anger dimensions and incident cerebrovascular disease may be mediated, in part, by increased atherosclerotic disease.

Age Factors↗
PubMedDate not supplied

Interleukin-6 covaries inversely with cognitive performance among middle-aged community volunteers.

OBJECTIVE: Recent evidence suggests that higher peripheral levels of interleukin 6 (IL-6) are associated with poorer cognitive function and predict future cognitive decline among the elderly. The current investigation extends the study of relationships between plasma IL-6 and cognitive performance to healthy middle-aged adults and to an examination of more specific cognitive domains. METHODS: Five hundred relatively healthy community volunteers aged 30 to 54 had blood drawn for the determination of plasma IL-6 levels and completed a battery of neuropsychological tests evaluating memory and executive function. RESULTS: After controlling for age, gender, race, and education, hierarchical regression analyses revealed an inverse relationship between circulating levels of IL-6 and performance on clusters of tests assessing auditory recognition memory, attention/working memory, and executive function. In contrast, there was no association between IL-6 and performance on tests of general memory. Secondary analyses demonstrated that relationships between IL-6 and auditory recognition and working memory and executive function were independent of a number of health factors, including body mass index, smoking, and hypertension. CONCLUSIONS: These findings contribute to a growing body of evidence linking chronic inflammation to poorer cognitive functioning and extend these findings to a midlife community sample, raising the possibility that IL-6 may represent a biomarker for risk of future cognitive decline.

Adult↗