Association of adiponectin with mortality in older adults: the Health, Aging, and Body Composition Study.

AIMS/HYPOTHESIS: Despite inverse associations with insulin resistance and adiposity, adiponectin has been associated with both increased and decreased risk of cardiovascular disease. We examined whether adiponectin is associated with total and cardiovascular mortality in older adults with well-characterised body composition. METHODS: We analysed data from 3,075 well-functioning adults aged 69-79 years at baseline. Mortality data were obtained over 6.6 +/- 1.6 years. We used Cox proportional hazards models adjusting for covariates in stages to examine the association between adiponectin and total and cardiovascular mortality. RESULTS: There were 679 deaths, 36% of which were from cardiovascular disease. Unadjusted levels of adiponectin were not associated with total or cardiovascular mortality. However, after adjusting for sex and race, adiponectin was associated with an increased risk of both total mortality (hazard ratio 1.26, 95% CI 1.15-1.37, per SD) and cardiovascular mortality (hazard ratio 1.35, 95% CI 1.17-1.56, per SD). Further adjustment for study site, smoking, hypertension, diabetes, prevalent heart disease, HDL-cholesterol, LDL-cholesterol, renal function, fasting insulin, triacylglycerol, BMI, visceral fat, thigh intermuscular fat and thigh muscle area did not attenuate this association. This association between adiponectin and increased mortality risk did not vary by sex, race, body composition, diabetes, prevalent cardiovascular disease, smoking or weight loss. CONCLUSIONS/INTERPRETATION: Higher levels of adiponectin were associated with increased risks of total and cardiovascular mortality in this study of older persons.

Location specific radiographic joint space width for osteoarthritis progression.

OBJECTIVE: To establish the performance of location specific computer measures of radiographic joint space width (JSW) compared to measurements of minimum joint space width (mJSW) for the assessment of medial compartment knee osteoarthritis (OA). The study also investigated the most disease-responsive location for measuring medial compartment JSW. METHODS: Serial bilateral Posterior Anterior (PA) conventional radiographs acquired with a fixed flexion protocol were obtained 36 months apart in 118 persons with knee OA participating in the Health, Aging and Body Composition (Health ABC) Study. Measurements of medial compartment mJSW and JSW at seven fixed locations were facilitated by the use of semi-automated software that delineated the femoral and tibial margins of the joint. A human reader operated custom software to verify and correct the software-drawn margins where necessary. Paired images were displayed with the reader blinded to the chronological order. The amount of joint space narrowing was measured and the standardized response mean (SRM) was used as a metric to quantify performance. RESULTS: For all subjects, the mJSW SRM value was 0.42 while, for the most responsive location specific measure of JSW, it was SRM=0.46. For subjects with a Kellgren-Lawrence (KL) score less than or equal to 1, mJSW (SRM=0.40) was more responsive than the new measures (Maximum SRM=0.30). For KL=2or3, SRM=0.49 for mJSW, and SRM=0.74 for the most responsive location specific measure of JSW. Improved responsiveness was observed in the more central portion of the joint on the more diseased knees. CONCLUSIONS: Location specific computer measures of JSW are feasible and potentially provide a superior method to assess radiographic OA for more diseased subjects. This new measure has the potential to improve the power of clinical studies that use a fixed flexion protocol.

Polymorphisms of angiotensinogen and angiotensin-converting enzyme associated with lower extremity arterial disease in the Health, Aging and Body Composition study.

The role of renin-angiotensin system (RAS) genes on the risk of lower extremity arterial disease (LEAD) in elderly people remains unclear. We assessed the relationship of genetic polymorphisms in RAS: G-6A, T174M and M235T of the angiotensinogen (AGT) gene, and the angiotensin-converting enzyme insertion/deletion (ACE_I/D) variant to the risk of LEAD in the Health, Aging and Body Composition (Health ABC) Study. This analysis included 1228 black and 1306 white men and women whose age ranged between 70 and 79 years at the study enrollment. LEAD was defined as ankle-arm index (AAI) <0.9. Genotype-phenotype associations were estimated by regression analyses with and without adjustment for established cardiovascular disease (CVD) risk factors. The proportion of LEAD was significantly higher in black (21.1%) than that in white elderly people (10.1%, P<0.0001). The distribution of AGT polymorphisms was also significantly different between black and white participants. There was no statistically significant association between the selected RAS genetic variants and LEAD after adjustment for age, antihypertensive medications, lipid-lowering medication, pack-year smoking, body mass index, low-density lipoprotein cholesterol, and prevalent diabetes and coronary heart disease. However, A-T haplotype of G-6A and M235T interacting with homozygous ACE_II (beta=-1.07, P=0.006) and with ACE inhibitors (beta=-1.03, P=0.01) significantly decreased the risk of LEAD in white but not in black participants after adjustment for the selected CVD risk factors. In conclusion, the study observed a gene-gene and gene-drug interaction for LEAD in the white elderly.

Efficacy of nonpharmacologic interventions in adults with high-normal blood pressure: results from phase 1 of the Trials of Hypertension Prevention. Trials of Hypertension Prevention Collaborative Research Group.

Phase 1 of the Trials of Hypertension Prevention was conducted in 2182 adults, aged 35-54 y, with diastolic blood pressure of 80-89 mm Hg to test the feasibility and blood pressure-lowering effects of seven nonpharmacologic interventions (weight loss, sodium reduction, stress management, and supplementation with calcium, magnesium, potassium, and fish oil). At 6 and 18 mo, weight loss and sodium reduction were well-tolerated and produced significant declines in systolic and diastolic blood pressures (-2.9/-2.4 and -2.1/-1.2 mm Hg for weight loss and sodium reduction, respectively, at 18 mo). None of the other interventions lowered blood pressure significantly at either the 6- or 18-mo follow-up visits. These results suggest that both weight loss and sodium reduction provide an effective means to prevent hypertension. The long-term effects of both of these interventions are being tested in phase 2 of the trial.

Recruitment for phase II of the Trials of Hypertension Prevention. Effective strategies and predictors of randomization. Trials of Hypertension Prevention (TOHP) Collaborative Research Group.

Phase II of the Trials of Hypertension Prevention is a multicenter, randomized, controlled trial designed to determine the efficacy of weight loss and reduction of sodium intake for lowering blood pressure and incidence of hypertension among persons with high-normal levels of blood pressure. The 2 x 2 factorial study design includes weight loss alone, restricted sodium intake alone, the combination of weight loss and sodium restriction, and a control group. Nine clinical centers used a variety of recruitment strategies to enroll 2382 participants over 17 months, which exceeded the sample size goal of 2250. Among randomized participants, 21% were minorities and 34% were women. Overall, direct mail generated the most randomized participants (73%), followed by community screening (12%) and media advertisement (11%). Referrals from community health care providers yielded few participants. Prescreening improved overall efficiency and reduced costs. Participants who were more likely to drop out voluntarily during the three-visit screening regimen tended to be younger, single, male, smokers, and less educated.

Trials of hypertension prevention. Phase I design.

Phase I of the Trials of Hypertension Prevention (TOHP) was a National Heart, Lung, and Blood Institute-sponsored, 3-year, national, multicenter, randomized, controlled trial designed to test the feasibility and efficacy of three life-style (weight loss, sodium restriction, and stress management) and four nutrition supplement (calcium, magnesium, fish oil, and potassium) interventions aimed at lowering diastolic blood pressure in those whose blood pressure was initially in the high normal range (80 to 89 mm Hg). A total of 2182 volunteers were recruited and allocated to the various treatment arms, such that each hypothesis was tested with a power of 85% or higher to detect a diastolic blood pressure treatment effect of 2 mm Hg. The four nutrition supplement interventions were delivered in a double-blinded fashion and the three life-style interventions, single (observed) -blinded. Phase I was designed to provide a rigorous test of short-term lowering of blood pressure for each of the seven treatments chosen and provides the basis for planning of a subsequent long-term trial of hypertension prevention.

The effect of potassium supplementation in persons with a high-normal blood pressure. Results from phase I of the Trials of Hypertension Prevention (TOHP). Trials of Hypertension Prevention (TOHP) Collaborative Research Group.

We conducted a randomized, double-blind, placebo-controlled trial of oral potassium chloride supplementation (60 mmol/d) in 353 men and women with an initial average diastolic blood pressure between 80 and 89 mm Hg. In the active (n = 178) compared to the placebo (n = 175) treatment group, the urinary potassium level was significantly (p < 0.001) increased by an average of 44.0 and 42.3 mmol/24 h following 3 and 6 months of therapy, respectively. Compared to placebo, active treatment was associated with a small (mean = 1.8 mm Hg) but significant (p = 0.04) reduction in diastolic blood pressure following 3 months of therapy. Following 6 months, however, this apparent treatment effect had virtually disappeared (mean reduction in diastolic blood pressure = 0.3 mm Hg). There was no significant effect of potassium supplementation on systolic blood pressure at either follow-up visit. There was a significant, independent, dose-response relationship between change in both 24-hour urinary potassium excretion and urinary sodium-potassium ratio and the corresponding change in diastolic blood pressure (-1.49 mm Hg for the highest versus the lowest quartile of change in urinary potassium excretion.

Misclassification and under-reporting of acute myocardial infarction by elderly persons: implications for community-based observational studies and clinical trials.

We investigated the accuracy of self-report of hospitalization for acute myocardial infarction (MI) by elderly persons in a community-based prospective study. Among 3809 persons aged 65 years or older followed up for 6 years, self-reported hospitalization for MI was validated by review of primary records and Medicare diagnoses. Among 147 who self-reported MI and for whom hospital records were available, the diagnosis was confirmed in 79 (54%). Myocardial infarction was not a reason for hospitalization among the remaining 68 participants; misclassification with other cardiovascular diagnoses was common. Medicare diagnosis correlated well with primary hospital records. Using Medicare diagnoses as the standard, the diagnosis of MI was confirmed in 53% of self-reports; the sensitivity and specificity of self-report were 51% and 98%, respectively. False-negative reporting was common because only half of hospitalizations for MI were reported. Self-report of hospitalization for MI by elderly persons in the community may be unreliable for ascertaining trends in cardiovascular diseases.

Airflow limitation is underrecognized in well-functioning older people.

OBJECTIVES: Dyspnea is a common symptom in older people. A reduced forced expiratory volume in 1 second (FEV1) is associated with a higher mortality rate from cardiovascular and respiratory disease, and increased admissions to hospitals. Underrecognized or undertreated airflow limitation may exacerbate the problem. The purpose of this study was to assess the prevalence and treatment of airflow limitation in a cohort of well-functioning older people. DESIGN: Cross-sectional study. SETTING: Baseline of a clinical-epidemiological study of incident functional limitation. PARTICIPANTS: Participants attended the baseline examination of the Health, Aging, and Body Composition study, a prospective cohort study of 3,075 well-functioning subjects age 70 to 79. MEASUREMENTS: Demographic and clinical data were collected by interview. Spirometry was performed unless contraindicated and repeated until three acceptable sets of flow-volume loops were obtained. Patients on bronchodilator medications had spirometry performed posttherapy. Blinded readers assessed the flow-volume loops, and inadequate tests were omitted from analysis. Airflow limitation was defined as a reduced forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) as determined by age-, sex-, and race-normalized values. Severity of airflow limitation was defined by American Thoracic Society criteria. RESULTS: Two thousand four hundred eighty-five subjects (80.8%) had assessable spirometry and data on treatment and diagnosis (1,265 men, 1,220 women). The mean age was 73.6 years. Two hundred sixty-two subjects (10.5%) had airflow limitation; 43 (16.4%) of these never smoked. Only 37.4% of participants with airflow limitation and 55.6% of participants with severe airflow limitation reported a diagnosis of lung disease. Only 20.5% of subjects with at least moderate airflow limitation had used a bronchodilator in the previous 2 weeks. CONCLUSION: Despite their good functional status, airflow limitation was present, and underrecognized, in a considerable proportion of our older population. The low bronchodilator use suggests a significant reservoir of untreated disease. Physicians caring for older people need to be more vigilant for both the presence, and the need for treatment, of airflow limitation.

Baseline characteristics of participants in the Physicians' Health Study: a randomized trial of aspirin and beta-carotene in U.S. physicians.

The Physicians' Health Study is a randomized, double-blind, placebo-controlled trial of primary prevention designed to assess the effects of low-dose aspirin on cardiovascular disease and of beta-carotene on risks of cancer. A total of 22,071 U.S. male physicians 40 to 84 years of age were randomized to one of four treatment groups: active aspirin and active beta-carotene, active aspirin and beta-carotene placebo, aspirin placebo and active beta-carotene, or both placebos. Whereas the beta-carotene component of the trial is ongoing, the blinded aspirin component was terminated early primarily because of a statistically extreme benefit of aspirin on first myocardial infarction. We obtained data relating to a large number of variables, including demographics, personal medical history, family history, health habits, and diet before randomization and compared them among the four treatment groups. As expected in a randomized trial of this sample size, the distribution of baseline characteristics was virtually identical among the treatment groups. This comparison indicates certainly no confounding by the baseline variables that were collected and suggests that other unmeasured or unknown potential confounders are also likely to be distributed evenly between the treatment groups. Thus, any observed differences in outcome between these groups likely result from the effects of the treatments themselves.

Recruitment for phase I of the trials of hypertension prevention.

Phase I of the Trials of Hypertension Prevention was a multicenter, randomized, controlled trial designed to determine the efficacy of seven nonpharmacologic interventions in reducing blood pressure among persons with high-normal diastolic blood pressure. The initial goal for recruitment was to enroll 2,100 participants over a nine-month period. The two major strategies for reaching potential participants were direct mailings and work site screenings. The yield from the first screening visit to randomization was 13% overall, with clinic-specific yields ranging from 4.5% to 31.7%. After five months of recruitment, approximately 60% of the goal for that point in the recruitment timetable had been randomized. Clinical centers falling short of their goals at that time altered their recruitment strategies and intensified their efforts, and centers that had exceeded their goals recruited additional participants. As a result, 2,182 participants, or 104% of the goal for recruitment, were randomized over a 13-month period. Those clinics using a cohort, or wave, type of enrollment were most successful in achieving their recruitment goals within the prescribed timetable.

Biochemical markers of compliance in the Physicians' Health Study.

The Physicians' Health Study is a randomized, double-blind, placebo-controlled trial using a 2 x 2 factorial design to test the effects of low-dose aspirin on risk of cardiovascular disease and beta-carotene supplementation on the incidence of cancer. To evaluate self-reported compliance with assigned treatment, we measured serum thromboxane B2, which is decreased after aspirin use, and plasma beta-carotene in samples of study participants drawn from three geographic locations in three different time periods. Thromboxane B2 levels were markedly lower in those assigned to aspirin (median = 63.5 pg/mL) than in those given aspirin placebo (median = 3,600 pg/mL, P less than .0001). Similarly, those assigned to beta-carotene had significantly higher levels (median = 1,176 ng/mL) than those given placebo (median = 306 ng/mL, P less than .0001). In addition, there was a highly significant positive correlation between levels of these biochemical markers and the self-reports of compliance (r = 0.65 for thromboxane B2 and r = 0.69 for beta-carotene, P less than .0001). These findings support the validity of the self-reported compliance in the Physicians' Health Study.

Clinical experience in 82 patients with pancreas divisum: preliminary results of manometry and endoscopic therapy.

Although it is clear that the majority of patients with pancreas divisum have no clinical disease, there is a subset of patients who have either unexplained abdominal pain or recurrent pancreatitis. Endoscopic therapy of the minor papilla may alter the clinical course of those patients with pancreas divisum and recurrent pancreatitis. Manometric study of the minor papilla is feasible and reveals a sphincter mechanism similar to the major papilla. Clinical response to endoscopic therapy may aid in selecting patients who might benefit from surgical sphincteroplasty. Refinement of manometric study of the minor papilla offers a potential method of detecting functional obstruction of dorsal duct drainage.

Auditory elicitation of the P300 event-related evoked potential in the rat.

Auditory stimuli were used to elicit a P300 event-related evoked potential (ERP) in rat. Test conditions were comparable to those for eliciting ERP's in humans. A train of background tones with a randomly inserted target tone at a ten to one ratio were presented individually to ten unrestrained subjects in a baseline, a novel, and a trained condition. In the novel condition EEG's were averaged from subjects hearing both background and target stimuli for the first time. In the trained condition, subjects were previously trained using footshock in a shuttle box to discriminate the target tone. A statistical comparison of an ERP peak elicited at approximately 300 msec in both the novel and target condition compared with the baseline demonstrated the presence of the P300 in the rat.

Do sweat calcium losses affect bone mass during firefighter training?

Although participation in vigorous exercise is associated with increased bone mass, recent evidence suggests that loss of calcium in sweat may result in a negative calcium balance and, ultimately, a decrease in bone mass. Anthropometric characteristics, habitual physical activity levels, dietary calcium intake, bone mineral content, and bone turnover markers were measured in 42 male recruits before and after 4 months of firefighter training. During two strenuous mid-training sessions, sweat calcium concentrations were measured; they averaged 1.1 mM. Whole body and total hip bone mineral content increased significantly, as did one marker of bone formation, and were not associated with sweat calcium concentration. This study demonstrates that intense physical training sessions that produce high sweat rates do not have an adverse effect on the bone mineral content of healthy young men.

Common sexual problems of children and adolescents.

The pediatrician is often expected by families to deal with sexual problems of children and adolescents. The physician should be able to identify problems and to guide parents in more meaningful communication and education of their children. Hopefully, he will be able to identify family conflicts and make the appropriate intervention or referral. He should be aware of his own sexual attitudes so as to avoid having his bias interfere with treatment. The childs behavior should not be isolated, but considered in the context of his family, his peers, and his own growth and development. Often, it is more useful to advise the family than to work with a young child. Adolescents present particular problems because of their conflicts over sexual identity, their reluctance to admit to problems, and frequently a mistrust of adults. They often feel a need for a trusting relationship with an adult, however, and are able to relate to a sensitive, non-judgmental professional.

Risk factors for septicemia-associated mortality in older adults.

Septicemia is the 10th leading cause of death among older adults in the United States; its mortality rate has steadily increased over the past decades. Little is known about factors which predispose to septicemia mortality in the elderly. The authors investigated risk factors for septicemia-associated mortality in 10,269 older adults as part of a longitudinal study of three communities (East Boston, MA; New Haven, CT; and Iowa and Washington Counties, IA). During 6 years of followup, 177 persons (3.2 per 1,000 person-years) had septicemia ICD9 038 (International Classification of Diseases, ninth revision) reported on their death certificate. In a multivariate proportional-hazards model, septicemia mortality was significantly (P < 0.05) and independently associated with age, male sex, history of diabetes, history of cancer requiring hospitalization, smoking one pack of cigarettes per day or more, not drinking alcohol in the year prior to baseline, disability in activities of daily living, cognitive impairment, and missing cognitive testing score. These factors might be useful in developing an at-risk population for testing septicemia treatment or prevention strategies in a community setting. Further investigation is needed to explain underlying mechanisms of increased risk of subsequent septicemia.

Disability and cognitive impairment are risk factors for pneumonia-related mortality in older adults.

The role of functional and cognitive limitations in the risk of pneumonia-related mortality in older adults was examined. As part of a cohort study in 3 communities (East Boston, MA; New Haven, CT; and Iowa and Washington Counties, IA), 6,234 women and 4,035 men ages 65 or older completed baseline interviews between 1981 and 1983 and were followed for up to 6 years. Sex-specific Cox proportional-hazards regression models were used to examine the association of baseline physical and cognitive functioning with report of pneumonia (ICD9 480-486) as an underlying, immediate, or contributing cause of death. During followup, a total of 243 men and 160 women died with pneumonia. Adjusting for age, race, education, evidence of five chronic diseases, and smoking status, a significantly increased risk of pneumonia mortality (P < 0.05) was found for limitations in activities of daily living and cognitive impairment among both men and women. Inability to walk a half mile, climb stairs, or perform heavy housework was significantly associated with increased risk of pneumonia mortality for women but not for men in the same multivariate models. Men and women whose body-mass index was above the median had significantly lower risk of pneumonia mortality compared with those in the lowest quartile. Further elucidation of the sequence between physical and cognitive impairment and risk of pneumonia will be important in reducing pneumonia-associated morbidity and mortality.

Accelerating Scientific Discovery Through Computation and Visualization.

The rate of scientific discovery can be accelerated through computation and visualization. This acceleration results from the synergy of expertise, computing tools, and hardware for enabling high-performance computation, information science, and visualization that is provided by a team of computation and visualization scientists collaborating in a peer-to-peer effort with the research scientists. In the context of this discussion, high performance refers to capabilities beyond the current state of the art in desktop computing. To be effective in this arena, a team comprising a critical mass of talent, parallel computing techniques, visualization algorithms, advanced visualization hardware, and a recurring investment is required to stay beyond the desktop capabilities. This article describes, through examples, how the Scientific Applications and Visualization Group (SAVG) at NIST has utilized high performance parallel computing and visualization to accelerate condensate modeling, (2) fluid flow in porous materials and in other complex geometries, (3) flows in suspensions, (4) x-ray absorption, (5) dielectric breakdown modeling, and (6) dendritic growth in alloys.

Plasma F2-isoprostane level and cognitive function over eight years in non-demented older adults: Findings from the Health ABC Study.

F2-isoprostanes (F2-IsoP) are reportedly increased in dementia patients, and are considered a reliable biomarker of oxidation. However, few studies have examined the predictive value of peripheral F2-IsoP levels in non-demented older adults. This study assesses the association between plasma F2-IsoP and change in cognitive function in non-demented elderly over eight years. Plasma F2-IsoP was measured by gas chromatography-mass spectrometry in a biracial cohort of 726 elderly men and women. Digit Symbol Substitution test and the Modified Mini-Mental State Exam were administered over time. No association was found between F2-IsoP tertile and baseline or change (slope) in cognitive function over eight years. Plasma F2-IsoP is not a valuable biomarker in predicting cognitive change over years in non-demented older adults.