Walter H. Ettinger

Associations of elevated interleukin-6 and C-reactive protein levels with mortality in the elderly.

PURPOSE To investigate whether interleukin-6 and C-reactive protein levels predict all-cause and cause-specific mortality in a population-based sample of nondisabled older people. SUBJECTS AND METHODS A sample of 1,293 healthy, nondisabled participants in the Iowa 65+ Rural Health Study was followed prospectively for a mean of 4.6 years. Plasma interleukin-6 and C-reactive protein levels were measured in specimens obtained from 1987 to 1989. RESULTS Higher interleukin-6 levels were associated with a twofold greater risk of death [relative risk (RR) for the highest quartile (> or = 3.19 pg/mL) compared with the lowest quartile of 1.9 [95% confidence interval, CI, 1.2 to 3.1]). Higher C-reactive protein levels (> or = 2.78 mg/L) were also associated with increased risk (RR = 1.6; CI, 1.0 to 2.6). Subjects with elevation of both interleukin-6 and C-reactive protein levels were 2.6 times more likely (CI, 1.6 to 4.3) to die during follow-up than those with low levels of both measurements. Similar results were found for cardiovascular and noncardiovascular causes of death, as well as when subjects were stratified by sex, smoking status, and prior cardiovascular disease, and for both early (<2.3 years) and later follow-up. Results were independent of age, sex, body mass index, and history of smoking, diabetes, and cardiovascular disease, as well as known indicators of inflammation including fibrinogen and albumin levels and white blood cell count. CONCLUSIONS Higher circulating levels of interleukin-6 and C-reactive protein were associated with mortality in this population-based sample of healthy older persons. These measures may be useful for identification of high-risk subgroups for anti-inflammatory interventions.

Self‐Reported Causes of Physical Disability in Older People: The Cardiovascular Health Study

OBJECTIVE: To determine the major conditions and symptoms reported to cause difficulty in 17 physical tasks of daily life and the criterion validity of self‐report of diseases given as the causes of the difficulty in functioning, in community‐dwelling older people.

Exercise and weight loss in obese older adults with knee osteoarthritis: a preliminary study.

OBJECTIVE: The purposes of this pilot study were to determine if a combined dietary and exercise intervention would result in significant weight loss in older obese adults with knee osteoarthritis, and to compare the effects of exercise plus dietary therapy with exercise alone on gait, strength, knee pain, biomarkers of cartilage degradation, and physical function.

Physical disability in older adults: A physiological approach

Measures of physical function have been developed primarily to assess health status, prognosis, and service needs. They are now, increasingly, being used as outcome measures in studies seeking to determine the causes of disability. However, the extent to which these standardized measures, as they currently are constituted, are meaningful for the evaluation of underlying pathophysiology is not defined. To assess evidence for an etiologic rationale for these measures, we evaluated self-report of difficulty in physical function in the Cardiovascular Health Study, a study of 5201 men and women 65 years and older in four U.S. communities. We determined (by factor analysis) that self-reported difficulty with each of 17 tasks of daily life aggregates in four groups; i.e. difficulty in one task is associated with having difficulty in the other tasks in the group. These groups include (1) activities primarily dependent on mobility and exercise tolerance; (2) complex activities heavily dependent on cognition and sensory input; (3) selected basic self-care activities; and (4) upper extremity activities. Groups 2 and 3 are similar, but not identical, to Instrumental Activities of Daily Living (IADL) and Activities of Daily Living (ADL), respectively. We then tested whether these groupings were associated with different underlying impairments. Multiple logistic regression analyses indicate that there are constellations of physiologic and disease characteristics significantly (p < 0.01) associated with difficulty in each of these four groups of activities, among 15 chronic diseases and conditions ascertained. Some diseases are uniquely associated with difficulty in one group of tasks; some overlap, and are associated with 2, 3 or 4 groups of tasks. The associations found with difficulty in performing tasks in groups 2 and 3 were frequently stronger than those with the larger groups of ADL or IADL tasks, suggesting increased specificity of associations found with these new groupings. These results suggest that re-grouping of tasks of daily life may provide a more refined physiologically-based outcome measure for use in evaluating causes of disability. The ability to define risk factors for disability may be enhanced by choosing outcome measures with a demonstrated physiologic rationale.

Physical Activity, Functional Limitations, and Disability in Older Adults

OBJECTIVES: To explore initially how low levels of physical activity influence lower body functional limitations in participants of the Longitudinal Study of Aging. Changes in functional limitations are used subsequently to predict transitions in the activities of daily living/instrumental activities of daily living (ADL/IADL) disability, thus investigating a potential pathway for how physical activity may delay the onset of ADL/IADL disability and, thus, prolong independent living.

Assessing performance-related disability in patients with knee osteoarthritis

This investigation describes the development and validation of a test battery for evaluating physical activity restrictions (PAR) in patients with knee osteoarthritis (OA). The tasks on the final version of the PAR include (a) a 6-min walk; (b) a stair climb; (c) a lifting and carrying task; and (d) getting into and out of a car. Data from patients with knee OA revealed that the four tasks loaded highly on a single unrotated principal component yielding an alpha internal consistency reliability of 0.92. These data suggest that investigators may choose to use an aggregate score and/or responses from individual tasks. Two week test-retest reliabilities for the four tasks were all in excess of 0.85 and there was support for their concurrent and convergent validity. Specifically, performance on the tasks correlated with time on treadmill, difficulty with self-reported ADLs, and ratings of difficulty following the performance of each task. Additional research is needed on the predictive validity of the measure and its sensitivity to change.

Long-term physical functioning in persons with knee osteoarthritis from NHANES. I: Effects of comorbid medical conditions.

This study examined the effects of comorbid medical conditions (heart disease, pulmonary disease, hypertension and obesity) on the association of radiographic knee osteoarthritis (OA) with long-term difficulty in physical function. Data are from the National Health and Nutrition Examination Survey, 1971-1975 (NHANES I), a prospective epidemiologic cohort study, and the NHANES Epidemiologic Follow-up Study, 1982-1984 (NHEFS) and included 4059 persons who were 45-74 years old and participated in the detailed examination component of NHANES I. Knee OA was ascertained by anterior-posterior bilateral radiographs of the knee and self-report of knee pain, heart and pulmonary disease by self report of disease or symptoms, and hypertension and obesity by blood pressure and weight measurements. The presence of symptomatic knee OA at NHANES I was associated with reported difficulty at NHEFS 1982-84 in functions which used the lower extremity (ambulation and transfer). The presence of coexistent chronic conditions, particularly heart disease, pulmonary disease and obesity, increased the likelihood of subsequent disability. These findings suggest that knee OA is associated with long-term physical disability, and that the presence of coexistent chronic disease may increase the amount of long-term disability from knee OA.

Long‐Term Exercise and its Effect on Balance in Older, Osteoarthritic Adults: Results from the Fitness, Arthritis, and Seniors Trial (FAST)

OBJECTIVES: To examine the effects of 18‐month aerobic walking and strength training programs on static postural stability among older adults with knee osteoarthritis.

The Relationship of Fibrinogen and Factors VII and VIII to Incident Cardiovascular Disease and Death in the Elderly Results From the Cardiovascular Health Study

Little is known about the prospective associations of fibrinogen, factor VII, or factor VIII with cardiovascular disease (CVD) and mortality in the elderly. At baseline in the Cardiovascular Health Study (5888 white and African American men and women; aged >/=65 years), we measured fibrinogen, factor VIII, and factor VII. We used sex-stratified stepwise Cox survival analysis to determine relative risks (RRs) for CVD events and all-cause mortality (up to 5 years of follow-up), both unadjusted and adjusted for CVD risk factors and subclinical CVD. After adjustment, comparing the fifth quintile to the first, fibrinogen was significantly associated in men with coronary heart disease events (RR=2.1) and stroke or transient ischemic attack (RR=1.3), and also with mortality within 2.5 years of follow-up (RR=5.8) and later (RR=1.7). Factor VIII was significantly associated in men with coronary heart disease events (RR=1.5) and mortality (RR=1.8), and in women with stroke/transient ischemic attack (RR=1.4). For both factors, values were higher in those who died, whether causes were CVD-related or non-CVD-related, but highest in CVD death. Factor VII exhibited associations with incident angina (RR=1.44) in men and with death in women (RR, middle quintile compared with first=0.66). However, in general, factor VII was not consistently associated with CVD events in this population. We conclude that, if confirmed in other studies, the measurement of fibrinogen and/or factor VIII may help identify older individuals at higher risk for CVD events and mortality.

Obesity and osteoarthritis of the knee: Evidence from the national health and nutrition examination survey (NHANES I)

The importance of systemic/metabolic factors in the association of obesity with radiographic knee osteoarthritis (OA) was examined for 3,905 adults aged 45 to 74 from the United States National Health and Nutrition Examination Survey, 1971 to 1975 (NHANES I). Obesity was associated with both bilateral and unilateral OA, but more strongly with bilateral OA. Obesity was also associated with both symptomatic and nonsymptomatic knee OA. Controlling for age, sex, serum cholesterol, serum uric acid, diabetes, body fat distribution, bone density, and blood pressure did not significantly reduce the association between obesity and knee OA. Findings from these data are not supportive of a metabolic link between obesity and knee OA.