Predictive value of systolic and diastolic function for incident congestive heart failure in the elderly: the cardiovascular health study.

OBJECTIVES: We sought to assess the ability of echocardiographic indices of systolic and diastolic function to predict incident congestive heart failure (CHF). BACKGROUND: Noninvasive indices of subclinical systolic and/or diastolic dysfunction that can be used to identify patients in a transition phase between normal cardiac function and clinical CHF would be valuable. Though midwall shortening and Doppler mitral inflow patterns are seemingly well suited to predict subsequent CHF, the predictive value of these indices has not been investigated. METHODS: We studied 2,671 participants in the Cardiovascular Health Study who were free of coronary heart disease, CHF or atrial fibrillation. Clinical and quantitative echocardiographic data were obtained in all participants. RESULTS: At a mean follow-up of 5.2 years (range 0 to 6 years), 170 participants (6.4% of the cohort) developed CHF. Although 96% of these participants had normal or borderline ejection fraction (EF) at baseline, only 57% had normal or borderline EF at the time of hospitalization. In multivariate modeling, fractional shortening at the endocardium (relative risk [RR] 1.85 per 10-unit decrease, confidence interval [CI] 1.27 to 2.39), fractional shortening at the midwall (RR 1.29 per five-unit decrease, 95% CI 1.11-1.51) and peak Doppler peak E (RR 1.15 for each 0.1 M/s increment; CI 1.02 to 1.21) independently predicted incident CHF. Both high and low Doppler E/A ratios were predictive of incident CHF. CONCLUSIONS: Roughly half the occurrences of CHF in this population are associated with normal or borderline EF. Echocardiographic findings suggestive of subclinical contractile dysfunction and diastolic filling abnormalities are both predictive of subsequent CHF. The standard (FSendo) and refined (FSmw) parameters of systolic function performed similarly in this regard, though subjects with left ventricular hypertrophy and depressed FSmw are at particularly high risk for subsequent CHF.

Tobacco, hypertension, and vascular disease: risk factors for renal functional decline in an older population.

BACKGROUND: A decline in renal function with age has been noted in some but not all individuals. The purpose of this study was to identify risk factors associated with a clinically significant increase in serum creatinine (of at least 0.3 mg/dL) in an older nondiabetic population. METHODS: A retrospective case-control study was performed analyzing data obtained from 4142 nondiabetic participants of the Cardiovascular Health Study Cohort, all at least 65 years of age, who had two measurements of serum creatinine performed at least three years apart. Cases were identified as participants who developed an increase in serum creatinine of at least 0.3 mg/dL, with controls including participants who did not sustain such an increase. RESULTS: There was an increase in the serum creatinine of at least 0.3 mg/dL in 2.8% of the population. In a multivariate "best-fit" model adjusted for gender, weight, black race, baseline serum creatinine, and age, the following factors were associated with an increase in serum creatinine: number of cigarettes smoked per day, systolic blood pressure, and maximum internal carotid artery intimal thickness. CONCLUSIONS: These data suggest that three very preventable or treatable conditions-hypertension, smoking, and prevalent vascular disease, which are associated with large and small vessel disease-are highly associated with clinically important changes in renal function in an older population.

The role of APOE epsilon4 in modulating effects of other risk factors for cognitive decline in elderly persons.

CONTEXT: Cognitive decline in elderly persons is often an early predictor of dementia. Subclinical cardiovascular disease (CVD) and diabetes mellitus may contribute to substantial decline in cognitive function in the elderly. These risks may be modified by gene-environment interactions between apolipoprotein E (APOE) genotype and CVD risk factors or subclinical CVD. OBJECTIVES: To examine the association between subclinical CVD and decline in cognitive functioning in the elderly and to examine effect modification by the APOE genotype of the association between subclinical disease and cognitive decline. DESIGN: The Cardiovascular Health Study, a population-based, prospective cohort study. SETTING AND POPULATION: A total of 5888 randomly selected Medicare-eligible participants from Sacramento County, California; Forsyth County, North Carolina; Washington County, Maryland; and Pittsburgh, Pa, aged 65 years or older, who were recruited in 1989-1990 (n = 5201) and in 1992-1993 (n = 687) and who were followed up for 7 and 5 years, respectively. MAIN OUTCOME MEASURES: Change over time in scores on the Modified Mini-Mental State Examination and the Digit Symbol Substitution Test as a function of APOE genotype, subclinical CVD, and diabetes mellitus. RESULTS: Seventy percent of participants had no significant decline on the Modified Mini-Mental State Examination. Systolic blood pressure, the ankle-arm brachial index, atherosclerosis of the internal carotid artery, diabetes mellitus, and several diagnoses of prevalent CVD were significantly associated with declines in scores on the Modified Mini-Mental State Examination and the Digit Symbol Substitution Test. The rate of cognitive decline associated with peripheral vascular disease, atherosclerosis of the common and internal carotid arteries, or diabetes mellitus was increased by the presence of any APOE epsilon4 allele. CONCLUSIONS: Most healthy elderly people did not experience cognitive decline. Measures of subclinical CVD were modest predictors of cognitive decline. Those with any APOE epsilon4 allele in combination with atherosclerosis, peripheral vascular disease, or diabetes mellitus were at substantially higher risk of cognitive decline than those without the APOE epsilon4 allele or subclinical CVD. High levels of atherosclerosis increased cognitive decline independently of APOE genotype.

Ankle-arm index as a predictor of cardiovascular disease and mortality in the Cardiovascular Health Study. The Cardiovascular Health Study Group.

Peripheral arterial disease (PAD) in the legs, measured noninvasively by the ankle-arm index (AAI) is associated with clinically manifest cardiovascular disease (CVD) and its risk factors. To determine risk of total mortality, coronary heart disease, or stroke mortality and incident versus recurrent CVD associated with a low AAI, we examined the relationship of the AAI to subsequent CVD events in 5888 older adults with and without CVD. The AAI was measured in 5888 participants >/=65 years old at the baseline examination of the Cardiovascular Health Study. All participants had a detailed assessment of prevalent CVD and were contacted every 6 months for total mortality and CVD events (including CVD mortality, fatal and nonfatal myocardial infarction, congestive heart failure, angina, stroke, and hospitalized PAD). The crude mortality rate at 6 years was highest (32.3%) in those participants with prevalent CVD and a low AAI (P<0.9), and it was lowest in those with neither of these findings (8.7%, P<0.01). Similar patterns emerged from analysis of recurrent CVD and incident CVD. The risk for incident congestive heart failure (relative risk [RR]=1.61) and for total mortality (RR=1.62) in those without CVD at baseline but with a low AAI remained significantly elevated after adjustment for cardiovascular risk factors. Hospitalized PAD events occurred months to years after the AAI was measured, with an adjusted RR of 5.55 (95% CI, 3.08 to 9.98) in those at risk for incident events. A statistically significant decline in survival was seen at each 0.1 decrement in the AAI. An AAI of <0.9 is an independent risk factor for incident CVD, recurrent CVD, and mortality in this group of older adults in the Cardiovascular Health Study.

The effects of measurement error in response variables and tests of association of explanatory variables in change models.

Biomedical studies often measure variables with error. Examples in the literature include investigation of the association between the change in some outcome variable (blood pressure, cholesterol level etc.) and a set of explanatory variables (age, smoking status etc.). Typically, one fits linear regression models to investigate such associations. With the outcome variable measured with error, a problem occurs when we include the baseline value of the outcome variable as a covariate. In such instances, one can find a relationship between the observed change in the outcome and the explanatory variables even when there is no association between these variables and the true change in the outcome variable. We present a simple method of adjusting for a common measurement error bias that tends to be overlooked in the modelling of associations with change. Additional information (for example, replicates, instrumental variables) is needed to estimate the variance of the measurement error to perform this bias correction.

Asymptomatic internal carotid artery stenosis defined by ultrasound and the risk of subsequent stroke in the elderly. The Cardiovascular Health Study.

BACKGROUND AND PURPOSE: We sought in this study to relate carotid ultrasound findings in asymptomatic older adults to the 5-year risk of various cerebrovascular outcomes used in the Asymptomatic Carotid Atherosclerosis Study (ACAS). METHODS: The Cardiovascular Health Study (CHS) is a longitudinal study of people 65 years and older. Analyses of internal carotid artery stenosis defined by multiple different cutoffs of peak systolic velocity, rather than one particular cutoff, were performed in the 5441 participants who underwent carotid ultrasound and lacked a history of transient ischemic attack or stroke. The 5-year risks of 7 cerebrovascular disease outcomes used in ACAS were estimated for each cutoff. RESULTS: Associations with the 5-year risk of outcomes were substantially elevated only at cutoffs with high peak systolic velocities. In this population, the number of people with such high velocities was small. For example, with a cutoff of approximately 2.5 m/s, suggesting a stenosis of >70%, the 5-year risk of an ipsilateral fatal or nonfatal stroke was 5%, and only 0.5% of the group had velocities at least this high. CONCLUSIONS: In a group of older adults likely to participate in a screening program, as evidenced by willingness to participate in CHS, high peak systolic velocities consistent with high-grade carotid stenosis were uncommon and risk of subsequent cerebrovascular disease outcomes was relatively low. These findings do not suggest that similar populations of older adults would benefit from a program using ultrasound to screen for asymptomatic carotid stenosis.

Hypoechoic plaque at US of the carotid artery: an independent risk factor for incident stroke in adults aged 65 years or older. Cardiovascular Health Study.

PURPOSE: To investigate the association between incident (first) stroke and the echogenicity of internal carotid arterial plaque at ultrasonography (US). MATERIALS AND METHODS: A cohort of 4, 886 individuals who, at baseline, were 65 years of age or older and without symptoms of cerebrovascular disease was followed up for an average of 3.3 years. Baseline clinical findings were from color Doppler and duplex US studies of the carotid arteries and a record of traditional risk factors: age, sex, presence of diabetes mellitus, pack-years of cigarette smoking, presence of hypertension, elevated systolic and diastolic blood pressure, elevated low-density lipoprotein cholesterol level. RESULTS: Incident strokes, excluding hemorrhagic strokes and strokes of cardiac origin, were seen in 104 individuals (2.1%) at risk. Age- and sex-adjusted odds ratios for incident stroke were significant for hypoechoic plaque (odds ratio, 2.53; 95% CI, 1,42,4.53). After controlling for risk factors in a Cox proportional hazards model, the relative risk (RR) of incident stroke was 1.72 (p = .015) for hypoechoic plaque and 2.32 (P = .004) for internal carotid arterial narrowing of at least 50%. In addition, hypoechoic plaque (RR, 2.78; CI, 1.36,5.69) and 50%-100% stenosis (RR, 3.08; CI, 1.28, 7.41) were associated with ipsilateral, nonfatal stroke. CONCLUSION: In asymptomatic adults aged 65 years or older, that risk of incident stroke was associated with two US features: hypoechoic internal carotid arterial plaque and an estimated internal carotid arterial stenosis of 50%-100%.

Relationship between ApoE, MRI findings, and cognitive function in the Cardiovascular Health Study.

BACKGROUND AND PURPOSE: We determined the relationship between apolipoprotein (Apo)E, MRI, and low cognitive scores. METHODS: The relationship between age, education, ApoE genotype, MRI examination of the brain, subclinical and clinical cardiovascular disease, and low (<80) score on the Modified Mini-Mental State Examination (3MSE, as modified by Teng and Chui) was evaluated for 3469 black and white participants in the Cardiovascular Health Study (CHS) in years 5 and 6 of the study. The participants were followed for up to 3 years. RESULTS: The prevalence of scores <80 in years 5 and 6 of the CHS was 8.2% for participants without and 20.4% for those with prior history of stroke. Age, race, and education were important determinants of low 3MSE scores. The prevalence of ApoE-4 (odds ratio [OR], 1.6 [1.1 to 2.1]) was directly related to scores <80, as was high ventricular volume (OR, 1.6 [1.2 to 2.3]), high white matter grade (OR, 1.4 [1.1 to 1.9]), and infarctlike lesions (OR, 1.6 [1.2 to 2.1]) on the MRI in the multivariate analysis. A five-point or greater decline in scores over up to 3 years was more often observed for participants with low 3MSE scores at year 5, at older ages, with lower education, and experiencing incident stroke (OR, 3.6 [1.2 to 10.6]), ApoE-4 genotype (OR, 1.8 [1.4 to 2.3]), and with MRI findings of high ventricular volume (OR, 2.0 [1.5 to 2.7]), and infarctlike lesions (OR, 1.2 [0.9 to 1.5]). CONCLUSIONS: These results demonstrate that vascular changes on MRI, measures of brain atrophy, ApoE-4, and age, education, and race are associated with low cognitive scores among older individuals. The MRI of the brain provides valuable information related to cognitive tests and decline over time. The potential exists for using MRI measurements to identify high-risk individuals for dementia and to test potential interventions to reduce the risk of dementia.

Dietary assessment using a picture-sort approach.

Food-frequency questionnaires are usually administered as a list of foods to be checked off by the respondent or interviewer. Techniques in which participants sort into categories cards on which names or pictures of foods are printed can also be used to assess food intake. Food-frequency scores were obtained from a five-category picture sort administered to 4643 men and women aged > or = 65 y in the Cardiovascular Health Study (CHS). This one-step (qualitative) assessment yielded significant associations in expected directions between frequency scores and sex, age, race or ethnicity, body mass index, and use of a special diet. In the two-step (semiquantitative) version of this instrument, an interviewer documented specific frequencies and portion-size information for the foods in each sorting category. A substudy of the two-step version with 96 CHS participants indicated relative validity similar to that of conventionally administered food-frequency questionnaires. The one-step version may be broadly applicable to situations in which general food-pattern data can be informative and cost and time limitations are great. When it is feasible, the two-step picture sort may offer certain methodologic advantages because respondents have a chance to change their responses and the format may simplify the cognitive-response task. Sorting or picture-sort procedures deserve systematic attention in research on dietary assessment methods.

Subclinical disease as an independent risk factor for cardiovascular disease.

BACKGROUND: The primary aim of the present study was to determine the relation between measures of subclinical cardiovascular disease and the incidence of clinical cardiovascular disease among 5201 adults 65 years of age or older who were participating in the Cardiovascular Health Study. METHODS AND RESULTS: A new method of classifying subclinical disease at baseline examination in the Cardiovascular Health Study included measures of ankle-brachial blood pressure, carotid artery stenosis and wall thickness, ECG and echocardiographic abnormalities, and positive response to the Rose Angina and Claudication Questionnaire. Participants were followed for an average of 2.39 years (maximum, 3 years). For participants without evidence of clinical cardiovascular disease at baseline, the presence of subclinical disease compared with no subclinical disease was associated with a significant increased risk of incident total coronary heart disease including CHD deaths and nonfatal MI and angina pectoris for both men and women. For individuals with subclinical disease, the increased risk of total coronary heart disease was 2.0 for men and 2.5 for women, and the increased risk of total mortality was 2.9 for men and 1.7 for women. The increased risk changed little after adjustment for other risk factors, including lipoprotein levels, blood pressure, smoking, and diabetes. CONCLUSIONS: The measurement of subclinical disease provides an approach for identifying high-risk older individuals who may be candidates for more active intervention to prevent clinical disease.

Self-reported causes of physical disability in older people: the Cardiovascular Health Study. CHS Collaborative Research Group.

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. DESIGN: Cross sectional analyses of data obtained in an observational cohort study. SETTING: Research clinics in four US communities: Winston-Salem, NC, Hagerstown, MD, Pittsburgh, PA, and Sacramento, CA. PARTICIPANTS: 5201 community-dwelling people > or = 65 years old. RESULTS: Arthritis and other musculoskeletal diseases were given as the primary causes of difficulty in performing physical tasks by 49.0% of the participants reporting difficulty in any task, followed by heart disease (13.7%), injury (12.0%), old age (11.7%), lung disease (6.0%), and stroke (2.9%). The self-reports of diseases that caused disability varied by task. Whereas arthritis was given as a cause of difficulty in most of the 17 different tasks, heart and lung disease were more likely to be reported as causing difficulty with activities requiring high aerobic work capacity such as walking one-half mile or doing heavy housework. Stroke was more likely to be reported as causing difficulty with use of the upper extremities and in performing basic activities of daily living. There was a high degree of consistency (91%) between the diseases and symptoms reported to cause disabilities. The percentage of people who reported a disease as the cause of their difficulty performing a task and had independent confirmation of the diagnosis was 85% in men and 71% in women, and varied according to type of disease and the individual's cognitive status and health status. CONCLUSION: These data suggest that age-related chronic diseases are important causes of disability in older people but that the type of disability is dependent on the underlying disease that causes the disability. Also, self-report of the cause of disability appears to be generally accurate but is influenced by gender, health status, and type of disease.

Eating patterns of community-dwelling older adults: the Cardiovascular Health Study.

We analyzed eating patterns of 4643 adults (1988 men and 2655 women) aged 65 years and older at the time of their enrollment in the Cardiovascular Health Study. Diet was assessed with a qualitative, picture-sort food frequency questionnaire along with supplemental questions on other eating pattern variables. Consumption of high fat foods and low fiber foods was more frequent in older participants, men, minorities, and persons with body mass index > or = 30 kg/m2 and less common among persons who reported following self-prescribed or medically prescribed special diets. Few associations of consumption of specific food groups with disease status were identified. Participants with coronary heart disease, diabetes, hypertension, and cardiovascular disease were significantly more likely to report following a special diet and using low-calorie or low-sodium food products, however. Although the percentage of participants with prevalent disease who reported following special diets was relatively low from a clinical perspective, it was sufficiently high to suggest that controlling for dietary modifications may be important when attempting to identify associations of diet with prevalent disease in older populations.

Associations of postmenopausal estrogen use with cardiovascular disease and its risk factors in older women. The CHS Collaborative Research Group.

BACKGROUND: Postmenopausal estrogen replacement therapy has been associated with favorable levels of cardiovascular disease risk factors, but these associations and the relations between estrogen use and subclinical disease have not been examined in large samples of older women. METHODS AND RESULTS: Present and past estrogen use was ascertained in 2955 women > or = 65 years old in the Cardiovascular Health Study, a study of risk factors for coronary heart disease and stroke in the elderly. Present estrogen use was reported by 12% of these women and past use by an additional 26.5%. Estrogen use (past or present) was strongly associated with lower low-density lipoprotein cholesterol, fibrinogen, glucose, insulin, obesity, and age and higher high-density lipoprotein cholesterol and socioeconomic status (all P < .0001). Estrogen users also had lower levels of subclinical disease as measured by carotid intimal-medial thickness, carotid stenosis grade, ECG left ventricular mass, and Doppler mitral peak flow velocities (each P < .02). Relations were similar in younger and older women (65 to 74 versus > or = 75 years) and smokers and nonsmokers and were unchanged after women with poor medication compliance were excluded. After adjustment for other factors, estrogen use was associated with decreased carotid wall thickness, although this association was of borderline significance after further adjustment for lipids. CONCLUSIONS: Postmenopausal estrogen use in this sample of older women was associated with favorable cardiovascular disease risk factor profiles and with lower measures of subclinical disease. These findings suggest that postmenopausal estrogen use may be associated with lower risk of cardiovascular disease in women well into the eighth decade of life.

Carcinoma of the cervix, stage III. Results of radiation therapy.

From April 1969 through December 1980, 203 patients with Stage III epidermoid carcinoma of the cervix were treated with radiation therapy with curative intent. The disease-free survival at 2, 5, and 10 years was 50%, 33%, and 27%, respectively. The survival was better for patients with Stage IIIB disease than for those with Stage IIIA disease. Eighty-eight patients were treated with external beam therapy only, and 115 received external beam and brachytherapy. The disease-free survival was better for the combination therapy group initially, but this difference was not sustained beyond 5 years. One hundred eight patients experienced recurrence within the irradiated field, for a locoregional recurrence rate of 53%. Twenty-seven patients had complications (13%). The complications were mild in 13 patients, moderate in 4 patients, and severe in 10 patients. A study was made of the relationship of the dose to Point A and the occurrence of complications. Similar analyses were made of the bladder and rectal doses and the subsequent occurrence of urinary and intestinal complications. In these analyses, the mean dose to Point A and the critical organs was higher for the groups of patients with complications than for those patients without complications. This relationship was also observed when the patients were stratified for treatment with either external beam plus brachytherapy or external beam therapy alone.