Calvin H. Hirsch

The Natural History of Functional Morbidity in Hospitalized Older Patients

This study provides data on changes in the functional status of older patients that are associated with acute hospitalization. Seventy‐one patients over the age of 74 admitted to the medical service of Stanford University Hospital between February and May 1987 received functional assessments covering seven domains: mobility, transfer, toileting, incontinence, feeding, grooming, and mental status. Assessments were obtained by report from the patients caregiver (or the patient when he or she lived alone) for 2 weeks before admission; from the patients nurse on day 2 of hospitalization and on the day before discharge; and again from the caregiver (or patient) 1 week after discharge. The sample had a mean age of 84, covered 37 Diagnostic Related Groups, and had a median length of stay of 8 days. Between baseline and day 2, statistically significant deteriorations occurred for the overall functional score and for the individual scores for mobility, transfer, toileting, feeding, and grooming. None of these scores improved significantly by discharge. In the case of mobility, 65% of the patients experienced a decline in score between baseline and day 2. Between day 2 and discharge, 67°/o showed no improvement, and another 10% deteriorated further. These data suggest that older patients may experience a burden of new and worsened functional impairment during hospitalization that improves at a much slower rate than the acute illness. An awareness of delayed functional recovery should influence discharge planning for older patients. Greater efforts to prevent functional decline in the hospitalized older patient may be warranted.

Health effects of caregiving: The caregiver health effects study: An ancillary study of the cardiovascular health study

We propose that two related sources of variability in studies of caregiving health effects contribute to an inconsistent pattern of findings: the sampling strategy used, and the definition of what constitutes caregiving. Samples are often recruited through selfreferral and are typically comprised of caregivers experiencing considerable distress. In this study, we examine the health effects of caregiving in large population-based samples of spousal caregivers and controls using a wide array of objective and self-report physical and mental health outcome measures. By applying different definitions of caregiving, we show that the magnitude of health effects attributable to caregiving can vary substantially, with the largest negative health effects observed among caregivers who characterize themselves as being strained. From an epidemiological perspective, our data show that approximately 80% of persons living with a spouse with a disability provide care to their spouse, but only half of care providers report mental or physical strain associated with caregiving.

Incidence, manifestations, and predictors of worsening white matter on serial cranial magnetic resonance imaging in the elderly: the Cardiovascular Health Study.

Background and Purpose— Magnetic resonance imaging (MRI) scans in the elderly commonly show white matter findings that may raise concerns. We sought to document incidence, manifestations, and predictors of worsening white matter grade on serial imaging. Methods— The Cardiovascular Health Study is a population-based, longitudinal study of 5888 people aged 65 years and older, of whom 1919 have had extensive initial and follow-up evaluations, including 2 MRI scans separated by 5 years. Scans were read without clinical information in standard side-by-side fashion to determine worsening white matter grade. Results— Worsening was evident in 538 participants (28%), mostly (85%) by 1 grade. Although similar at initial scan, participants with worsening white matter grade, compared with those without, experienced greater decline on modified Mini-Mental State examination and Digit-Symbol Substitution test (both P≤0.001) after controlling for potential confounding factors, including occurrence of transient ischemic attack or stroke between scans. Independent predictors of worsening white matter grade included cigarette smoking before initial scan and infarct on initial scan. Otherwise, predictors differed according to white matter grade on initial scan. For low initial grade, increased age, increased diastolic blood pressure, increased high-density lipoprotein cholesterol, and decreased low-density lipoprotein cholesterol were associated with increased risk of worsening. For high initial grade, any cardiovascular disease and low ankle–arm index were associated with decreased risk of worsening, whereas use of diuretics and statins were associated with increased risk. Conclusion— Worsening white matter grade on serial MRI scans in elderly is common, is associated with cognitive decline, and has complex relations with cardiovascular risk factors.

Association of Carotid Artery Intima-Media Thickness, Plaques, and C-Reactive Protein With Future Cardiovascular Disease and All-Cause Mortality The Cardiovascular Health Study

Background— Carotid atherosclerosis, measured as carotid intima-media thickness or as characteristics of plaques, has been linked to cardiovascular disease (CVD) and to C-reactive protein (CRP) levels. We investigated the relationship between carotid atherosclerosis and CRP and their joint roles in CVD prediction. Methods and Results— Of 5888 participants in the Cardiovascular Health Study, an observational study of adults aged ≥65 years, 5020 without baseline CVD were included in the analysis. They were followed up for as long as 12 years for CVD incidence and all-cause mortality after baseline ultrasound and CRP measurement. When CRP was elevated (>3 mg/L) among those with detectable atherosclerosis on ultrasound, there was a 72% (95% CI, 1.46 to 2.01) increased risk for CVD death and a 52% (95% CI, 1.37 to 1.68) increased risk for all-cause mortality. Elevated CRP in the absence of atherosclerosis did not increase CVD or all-cause mortality risk. The proportion of excess risk attributable to the interaction of high CRP and atherosclerosis was 54% for CVD death and 79% for all-cause mortality. Addition of CRP or carotid atherosclerosis to conventional risk factors modestly increased in the ability to predict CVD, as measured by the c statistic. Conclusions— In older adults, elevated CRP was associated with increased risk for CVD and all-cause mortality only in those with detectable atherosclerosis based on carotid ultrasound. Despite the significant associations of CRP and carotid atherosclerosis with CVD, these measures modestly improve the prediction of CVD outcomes after one accounts for the conventional risk factors.

Kidney Function as a Predictor of Noncardiovascular Mortality

Chronic kidney disease is associated with a higher risk for cardiovascular mortality, as well as all-cause mortality. Whether chronic kidney disease is a predictor of noncardiovascular mortality is less clear. To further explore the latter, the association of kidney function with total noncardiovascular mortality and cause-specific mortality was assessed in the Cardiovascular Health Study, a community-based cohort of older individuals. Kidney disease was assessed using cystatin C and estimated GFR in 4637 participants in 1992 to 1993. Participants were followed until June 30, 2001. Deaths were adjudicated as cardiovascular or noncardiovascular disease by committee, and an underlying cause of death was assigned. The associations of kidney function with total noncardiovascular mortality and cause-specific mortality were analyzed by proportional hazards regression. Noncardiovascular mortality rates increased with higher cystatin C quartiles (16.8, 17.1, 21.6, and 50.0 per 1000 person-years). The association of cystatin C with noncardiovascular mortality persisted after adjustment for demographic factors; the presence of diabetes, C-reactive protein, hemoglobin, and prevalent cardiovascular disease; and measures of atherosclerosis (hazard ratio 1.69; 95% confidence interval 1.33 to 2.15, for the fourth quartile versus the first quartile). Results for estimated GFR were similar. The risk for noncardiac deaths attributed to pulmonary disease, infection, cancer, and other causes was similarly associated with cystatin C levels. Kidney function predicts noncardiovascular mortality from multiple causes in the elderly. Further research is needed to understand the mechanisms and evaluate interventions to reduce the high mortality rate in chronic kidney disease.

Association Between Lower Digit Symbol Substitution Test Score and Slower Gait and Greater Risk of Mortality and of Developing Incident Disability in Well‐Functioning Older Adults

OBJECTIVES: To determine whether, in well‐functioning older adults, a lower score on the Digit Symbol Substitution Test (DSST) and slower gait are associated with greater risk of mortality and of developing incident disability independent of other risk factors, including brain structural abnormalities (white matter hyperintensities, brain infarcts, ventricular enlargement) and whether the combination of varying levels of DSST score and gait speed are associated with a greater risk of mortality and disability than low DSST or slow gait alone.

The Association of Bone Mineral Density and Depression in an Older Population

OBJECTIVE: To evaluate the association between bone mineral density (BMD) and measurements of depression in an older population.

POSTMENOPAUSAL HORMONE THERAPY AND REGIONAL BRAIN VOLUMES: THE WHIMS-MRI STUDY

Objectives: To determine whether menopausal hormone therapy (HT) affects regional brain volumes, including hippocampal and frontal regions. Methods: Brain MRI scans were obtained in a subset of 1,403 women aged 71–89 years who participated in the Women’s Health Initiative Memory Study (WHIMS). WHIMS was an ancillary study to the Women’s Health Initiative, which consisted of two randomized, placebo-controlled trials: 0.625 mg conjugated equine estrogens (CEE) with or without 2.5 mg medroxyprogesterone acetate (MPA) in one daily tablet. Scans were performed, on average, 3.0 years post-trial for the CEE + MPA trial and 1.4 years post-trial for the CEE-Alone trial; average on-trial follow-up intervals were 4.0 years for CEE + MPA and 5.6 years for CEE-Alone. Total brain, ventricular, hippocampal, and frontal lobe volumes, adjusted for age, clinic site, estimated intracranial volume, and dementia risk factors, were the main outcome variables. Results: Compared with placebo, covariate-adjusted mean frontal lobe volume was 2.37 cm3 lower among women assigned to HT (p = 0.004), mean hippocampal volume was slightly (0.10 cm3) lower (p = 0.05), and differences in total brain volume approached significance (p = 0.07). Results were similar for CEE + MPA and CEE-Alone. HT-associated reductions in hippocampal volumes were greatest in women with the lowest baseline Modified Mini-Mental State Examination scores (scores <90). Conclusions: Conjugated equine estrogens with or without MPA are associated with greater brain atrophy among women aged 65 years and older; however, the adverse effects are most evident in women experiencing cognitive deficits before initiating hormone therapy.

Longitudinal Changes in Thyroid Function in the Oldest Old and Survival: The Cardiovascular Health Study All-Stars Study

CONTEXT Data on thyroid function in the oldest old are sparse, and existing studies show conflicting evidence on the relationship between thyroid function and mortality in this age group. OBJECTIVE We describe longitudinal changes in thyroid function in a cohort of elderly individuals and determine the relationship between thyroid function and mortality. DESIGN, SETTING, AND PARTICIPANTS Eight hundred forty-three participants in the Cardiovascular Health Study All Stars Study who were not taking thyroid medications and had thyroid function testing in 2005-2006 (mean age 85 yr). MAIN OUTCOME MEASURE Thyroid-stimulating hormone (TSH), free T(4) (FT4), total T(3), and thyroid peroxidase antibody status were measured in 1992-1993 and 2005-2006. Deaths were ascertained through February 2011. RESULTS There was a statistically significant 13% increase in TSH, 1.7% increase in FT4, and 13% decrease in total T(3) over the 13-yr period. Two hundred eighty-seven deaths occurred over a median follow-up of 5.1 yr. There was no association between subclinical hypothyroidism[hazard ratio (HR) 0.97, 95% confidence interval (CI) 0.66-1.43], TSH level (HR per milliunits per liter 0.94, 95% CI 0.88-1.01), or persistent thyroid peroxidase antibody positivity (HR 1.09, 95% CI 0.62-1.92), and death. However, FT4 was positively associated with death (HR per nanograms per deciliter 2.57, 95% CI 1.32-5.02). CONCLUSIONS TSH increased over time in these older individuals. This elevation was not associated with increased or decreased mortality, although higher FT4 levels were associated with death. These findings raise concern for treatment of mild elevations of TSH in advanced age. Further studies are needed to determine the potential benefit of treating age-related changes in thyroid function.

Predictors of perceived health status in elderly men and women. The Cardiovascular Health Study.

Baseline data on the perceived health status of participants (N = 5,201) in the Cardiovascular Health Study of the Elderly (CHS) are reported. The authors examined the predictive utility of health-related factors representing eight different domains, assessed gender differences in the prediction of perceived health, and tested a hypothesis regarding the role of known clinical conditions versus subclinical disease in predicting perceived health. Multivariate analyses showed that the majority of the explained variance in self-assessed health is accounted for by variables that fall into four general categories. Although gender differences were small, the analysis showed that the relative importance of several predictor variables did vary by gender.