Plasma concentration of C-reactive protein and risk of ischemic stroke and transient ischemic attack: the Framingham study.

BACKGROUND: The role of C-reactive protein (CRP) as a novel plasma marker of atherothrombotic disease is currently under investigation. Previous studies have mostly related CRP to coronary heart disease, were often restricted to a case-control design, and failed to include pertinent risk factors to evaluate the joint and net effect of CRP on the outcome. We related plasma CRP levels to incidence of first ischemic stroke or transient ischemic attack (TIA) in the Framingham Study original cohort. METHODS: There were 591 men and 871 women free of stroke/TIA during their 1980 to 1982 clinic examinations, when their mean age was 69.7 years. CRP levels were measured by using an enzyme immunoassay on previously frozen serum samples. Analyses were based on sex-specific CRP quartiles. Risk ratios (RRs) were derived, and series of trend analyses were performed. RESULTS: During 12 to 14 years of follow-up, 196 ischemic strokes and TIAs occurred. Independent of age, men in the highest CRP quartile had 2 times the risk of ischemic stroke/TIA (RR=2.0, P=0.027), and women had almost 3 times the risk (RR=2.7, P=0.0003) compared with those in the lowest quartile. Assessment of the trend in risk across quartiles showed unadjusted risk increase for men (RR=1.347, P=0.0025) and women (RR=1.441, P=0.0001). After adjustment for smoking, total/HDL cholesterol, systolic blood pressure, and diabetes, the increase in risk across CRP quartiles remained statistically significant for both men (P=0.0365) and women (P=0.0084). CONCLUSIONS: Independent of other cardiovascular risk factors, elevated plasma CRP levels significantly predict the risk of future ischemic stroke and TIA in the elderly.

Elevated midlife blood pressure increases stroke risk in elderly persons: the Framingham Study.

BACKGROUND: Stroke risk predictions are traditionally based on current blood pressure (BP). The potential impact of a subject's past BP experience (antecedent BP) is unknown. We assessed the incremental impact of antecedent BP on the risk of ischemic stroke. METHODS: A total of 5197 stroke-free subjects (2330 men) in the community-based Framingham Study cohort were enrolled from September 29, 1948, to April 25, 1953, and followed up to December 31, 1998. We determined the 10-year risk of completed initial ischemic stroke for 60-, 70-, and 80-year-old subjects as a function of their current BP (at baseline), recent antecedent BP (average of readings at biennial examinations 1-9 years before baseline), and remote antecedent BP (average at biennial examinations 10-19 years earlier), with adjustment for smoking and diabetes mellitus. Models incorporating antecedent BP were also adjusted for baseline BP. The effect of each BP component (systolic BP, diastolic BP, and pulse pressure) was assessed separately. RESULTS: Four hundred ninety-one ischemic strokes (209 in men) were observed in eligible subjects. The antecedent BP influenced the 10-year stroke risk at the age of 60 years (relative risk per SD increment of recent antecedent systolic BP: women, 1.68 [95% confidence interval, 1.25-2.25]; and men, 1.92 [95% confidence interval, 1.39-2.66]) and at the age of 70 years (relative risk per SD increment of recent antecedent systolic BP: women, 1.66 [95% confidence interval, 1.28-2.14]; and men, 1.30 [95% confidence interval, 0.97-1.75]). This effect was evident for recent and remote antecedent BP, consistent in hypertensive and nonhypertensive subjects, and demonstrable for all BP components. CONCLUSIONS: Antecedent BP contributes to the future risk of ischemic stroke. Optimal prevention of late-life stroke will likely require control of midlife BP.

Longitudinal changes in the contribution of genetic and environmental influences to symptoms of depression in older male twins.

Genetically informative longitudinal data on self-reported symptoms of depression allow for an investigation of the causes of stability and change in depression symptoms throughout adult life. In this report, the authors investigated the relative contribution of genetic and environmental influences to symptoms of depression in 83 monozygotic and 84 dizygotic male twin pairs from the National Heart, Lung, and Blood Institute (NHLBI) Twin Study. Participants first completed the Center for Epidemiologic Studies-Depression (CES-D) scale in 1985-1986 and again during 1995-1997. Mean age of twins at baseline was 63 years, range 59 to 70. From cross-sectional genetic analyses we estimated the heritability of CES-D to be 25% (95% confidence interval [CI], 11%-39%) at baseline and 55% (95% CI, 40%-71%) at follow-up. Fitting longitudinal genetic models to the two-wave data, we found that stability of symptoms over the 10-year follow-up was due primarily to continuity of genetic influences.

The joint effect of apolipoprotein E epsilon4 and MRI findings on lower-extremity function and decline in cognitive function.

BACKGROUND: Cognitive decline and poor physical function are risk factors for disability in old age and may occur more often in subjects with the apolipoprotein E epsilon4 (ApoE-epsilon4) allele. The objective of this study was to investigate the joint effect of ApoE-epsilon4 and structural changes detected on MRI brain scans on cognitive decline and lower-extremity function. METHODS: Brain MRI (1.5 T), neuropsychological tests, and lower-extremity physical function tests were administered to World War II male veteran twins ages 69 to 80. Quantification of MRI scans used a previously published algorithm to segment brain images into total cerebral brain (TCB), cerebrospinal fluid (CSF), and white-matter hyperintensity (WMH) volumes. A short battery of physical performance tests was used to assess lower-extremity function. Ten-year changes in performance on the Mini-Mental State Exam (MMSE), the Benton Visual Retention Test (BVRT), and the Digit Symbol Substitution (DSS) test were used to assess cognitive decline. RESULTS: For the sample as a whole, the comparison of subjects by median split of total cerebral brain volume found that those with brain volumes below the median performed worse on tests of gait and balance (p < .01) and experienced greater cognitive decline on the MMSE and BVRT cognitive test batteries (both p < .01). In addition, subjects with WMH volumes above the median had poor performance on the standing balance tasks and experienced greater decline on the DSS test (p < .01). Stratified analyses revealed that the joint effect of radiological findings and the ApoE-epsilon4 allele on cognitive decline and lower-extremity function was often greater than that expected from the separate effects combined. CONCLUSIONS: We conclude that radiological findings in conjunction with ApoE-epsilon4 may single out a group at higher risk for dementia. We speculate that the observed interaction effect may be due to increased susceptibility to brain injury or impaired repair mechanisms in subjects with ApoE-epsilon4.

The contribution of genetic influences to measures of lower-extremity function in older male twins.

Tests of balance, gait, and endurance were administered to 95 monozygotic (MZ) and 92 dizygotic (DZ), white male twins aged 68 to 79 years who had been born in the United States. Within-twin-pair correlations were calculated for each individual task and for an overall summary performance score. These were subjected to structural equation modeling to determine the contributions of genetic and environmental influences to individual differences in performance scores. MZ intraclass correlations were significant and greater than DZ correlations for the 8-foot walk and the repeated chair stands task, but not for the standing balance task. The heritability of the lower-extremity summary score was 57%, of which 39% was due to additive genetic effects and 18% due to nonadditive effects. In addition, we found that genetic influences contributed primarily to twin similarity in the poorest quartile of performance, whereas shared environmental influences contributed to twin similarity in the best quartile.

Evidence for decline in disability and improved health among persons aged 55 to 70 years: the Framingham Heart Study.

OBJECTIVES: This study detected secular change in disability and health among persons aged 55 to 70 years, the life period when increases in disability and morbidity begin and retirement occurs. METHODS: Cross-sectional comparisons were completed with data from similarly aged members of the original (n = 1760) and offspring (n = 1688) cohorts of the Framingham Heart Study, which represent 2 generations. Analyses were conducted by gender and on chronic disease subgroups by logistic regression. RESULTS: There was substantially less disability in the offspring cohort than in the original cohort. Thirty-six percent of offspring men were disabled vs 52% of original cohort men (P = .001); among women, these proportions were 54% vs 72% (P = .001). Fewer offspring perceived their health as fair or poor and fewer had chronic diseases. Offspring were more physically active and less likely to smoke or consume high amounts of alcohol, but their average weight was greater. The secular decline in disability was strongly evident among individuals with chronic diseases. CONCLUSIONS: Our findings depict a secular change toward a less disabled and globally healthier population in the period of life when retirement occurs.

Preventive approach to poststroke rehabilitation in older people.

Stroke is the leading cause of adult neurologic-related disability. With the recent plateau in stroke death rates, the steady growth in the elderly population, and the secular trend toward more moderate levels of neurologic impairments, stroke continues to be a major health problem requiring rehabilitation interventions. For those who receive rehabilitation, the prognosis is good: most will walk, the greater percentage will be independent in activities of daily living, and only a small percentage will need institutionalization. Providing rehabilitation interventions that are timely, age-specific, and inclusive of treatment for all domains affected enhances potential recovery for elderly people.

Migrainous visual accompaniments are not rare in late life: the Framingham Study.

BACKGROUND AND PURPOSE: Questionnaires to elicit symptoms of transient ischemic attacks (TIAs) may detect late-life transient visual symptoms similar to the visual aura of migraine, often without headache. We determined the frequency, characteristics, and stroke outcome of these symptoms in the Framingham Study. METHODS: During 1971-1989, at biennial examinations, 2110 subjects of the Framingham cohort were systematically queried about the occurrence of sudden visual symptoms. RESULTS: Visual migrainous symptoms were reported by 1.23% (26/2110) of subjects (1.33% of women and 1.08% of men). In 65% of subjects the episodes were stereotyped, and they began after age 50 years in 77%. Mean +/- SD age at onset of the episodes was 56.2+/-18.7 years. In 58% of subjects the episodes were never accompanied by headaches, and 42% had no headache history. The number of episodes ranged from 1 to 500 and was 10 or more in 69% of subjects. The episodes lasted 15 to 60 minutes in 50% of subjects. Sixty-five percent of the subjects were examined by a study neurologist, and only 19% of them met the criteria of the International Headache Society. Twelve percent of subjects sustained a stroke after the onset of migrainous visual symptoms: a subarachnoid hemorrhage 1 year later, an atherothrombotic brain stem infarct 3 years later, and a cardioembolic stroke 27 years later. In contrast, of 87 subjects with TIAs in the same cohort, 33% developed a stroke (P = 0.030), two thirds within 6 months of TIA onset. CONCLUSIONS: Late-life-onset transient visual phenomena similar to the visual aura of migraine are not rare and often occur in the absence of headache. These symptoms appear not to be associated with an increased risk of stroke, and invasive diagnostic procedures or therapeutic measures are generally not indicated.

Survival and functional status 20 or more years after first stroke: the Framingham Study.

BACKGROUND AND PURPOSE: We examined the 20-or-more-year survival and functional levels of 148 stroke survivors and 148 age- and sex-matched control subjects from the Framingham Study Cohort, whom we originally studied in 1972-1974 to ascertain the survival and disability status of stroke survivors compared with that of controls. METHODS: This long-term evaluation was done with use of data from the 1993-1995 Framingham Study Cohort Examination 23 on the 10 stroke survivors and 20 control subjects still living to identify and compare the host characteristics and functional status of each group. The survival curves for both stroke survivors and controls were derived from the ongoing Framingham Study database. RESULTS: Twenty-plus-year stroke survivors experienced a greater mortality than age- and sex-matched controls (92.5% and 81%, respectively). The slopes of the two survival curves were essentially the same. Functional status (eg, walking and independence in activities of daily living) of stroke survivors, however, compared very favorably with that of the control subjects. Stroke survivors were more likely to be female and to have a number of comorbidities, including elevated blood pressures, greater use of medications, less use of alcohol, and less depressive symptomology. CONCLUSIONS: In the Framingham cohort, 20-plus-year stroke survivors showed greater mortality than age- and sex-matched control subjects; functionally, however, the groups were very similar and in general quite independent.

Intellectual decline after stroke: the Framingham Study.

BACKGROUND AND PURPOSE: The causes and characteristics of cognitive decline after stroke are poorly defined, because most studies have relied on the diagnosis of dementia after stroke, without measurement of prestroke cognitive function. METHODS: The Mini-Mental State Examination (MMSE) was used to assess the cognitive performance of 74 subjects from the Framingham Study cohort who had suffered a stroke during a 13-year period. We compared their poststroke cognitive performance with the prestroke MMSE scores collected during their biennial examinations, and their prestroke/poststroke changes in MMSE score were then compared with those of 74 control subjects matched for age and sex. Cases and controls underwent testing for symptoms of depression using the Center for Epidemiologic Studies of Depression (CES-D) scale, and these findings were correlated with their cognitive performance. Changes in cognitive performance in the cases were correlated with the CT-documented characteristics of the stroke. RESULTS: The cases had a significantly lower mean+/-SE MMSE score at prestroke baseline (27.28+/-0.34) than did the control subjects (28.08+/-0.21), a difference that became more pronounced (23.57+/-0.92 versus 28.31+/-0.25; P<.001) after stroke. The poststroke decline in cognitive function in the cases was correlated only with a large, left-sided stroke on CT. The CES-D scores were significantly higher in the cases, but nondepressed cases had significantly lower MMSE scores than nondepressed controls. CONCLUSIONS: Stroke is followed by a significant decline in cognitive performance when prestroke and poststroke measurements are compared. Although depression is more frequent in the stroke patients, their intellectual decline appears to be independent from the presence of depression.

Stroke severity in atrial fibrillation. The Framingham Study.

BACKGROUND AND PURPOSE: Stroke occurring with atrial fibrillation (AF) is more likely to be fatal or more severe than non-AF stroke based on clinical series, but data from prospective epidemiological studies are sparse and inconsistent. METHODS: Over 40-year follow-up of the original 5070 Framingham cohort, 501 initial ischemic strokes, including 103 with AF, were analyzed. Stroke severity was rated as none, mild, moderate, severe, or fatal. Since 1981, functional status indicated by the Barthel index has been evaluated acutely and at 3, 6, and 12 months. Severity and functional status of AF strokes were compared with non-AF strokes using chi 2 test and Student's t test. Thirty-day mortality was assessed by logistic regression analyses. RESULTS: AF was associated with increased stroke severity (P = .048). Thirty-day mortality was greater in AF strokes than in non-AF strokes (25% versus 14%). The multivariate-adjusted odds ratio for 30-day mortality for AF subjects was 1.84 (95% confidence interval, 1.04 to 3.27). Since 1981, follow-up was available for 150 initial ischemic strokes, including 30 with AF. Compared with the non-AF group, the AF group had poorer survival and more recurrences during 1 year of follow-up. The AF subjects had lower mean Barthel index scores acutely (29.6 versus 58.6, P < .001) and at 3 months (P = .005), 6 months (P = .003), and 12 months (P = .130) after stroke among survivors. CONCLUSIONS: Ischemic stroke associated with AF was nearly twice as likely to be fatal as non-AF stroke. Recurrence was more frequent, and functional deficits were more likely to be severe among survivors. Since stroke is usually the initial manifestation of embolism in AF, prevention is critical to reducing disability and mortality.

Temporal patterns of stroke onset. The Framingham Study.

BACKGROUND AND PURPOSE: Several studies have shown stroke onset to vary by season, day of the week, and time of day. These temporal patterns, which may provide insights into pathogenesis, were found mainly in clinical series, which can be subject to selection bias. To obtain a less distorted picture of stroke onset, we examined the month and season, day of the week, time, and place stroke occurred in a community-based cohort. METHODS: Over a 40-year period of surveillance of the Framingham Study cohort of 5070 people aged 30 to 62 years and free of stroke and cardiovascular disease at entry, 637 completed initial strokes occurred. Month, season, day of the week, time of day, and place of occurrence of stroke were ascertained systematically and related prospectively to stroke incidence, subtype, and gender. RESULTS: Winter was the peak season for cerebral embolic strokes. Significantly more stroke events occurred on Mondays than any other day, particularly for working men. For intracerebral hemorrhages, a third happened on Mondays in both genders. The time of day when strokes most frequently occurred was between 8 AM and noon. This pattern was true for all stroke subtypes. This pattern persisted when individuals whose onset occurred while sleeping or on awakening were excluded. Stroke in general occurred more at home, with hemorrhagic strokes occurring outside the home and cerebral embolisms in the hospital more than other subtypes. CONCLUSIONS: Temporal patterns of stroke onset were observed for season, day of the week, time of day, and place in a community-based population. These findings suggest that there are periods of increased risk of stroke that may be amenable to preventive strategies.

Development of health risk appraisal functions in the presence of multiple indicators: the Framingham Study nursing home institutionalization model.

A health risk appraisal function is a mathematical model designed to estimate the risk or probability of a person's mortality or morbidity for various diseases based upon risk factors such as age, medical history and smoking behaviour. The Framingham Study has contributed substantially to the development and use of these for endpoints such as mortality and incidence of coronary heart disease and other cardiovascular diseases. This paper discusses a methodology for the development of health risk appraisal functions when the number of potential risk factors is large and illustrates it with sex specific functions for nursing home institutionalization. The methodology involves grouping variables substantively into sets, applying principal component factor analysis and variable clustering to obtain substantively meaningful composite scores, ranking these in order of substantive importance, and then entering these with a hierarchical ordering into a Cox proportional hazard regression.

Assessment and psychologic factors in stroke rehabilitation.

With improved survival after stroke, it is important to identify those patients whose quality of life can be enhanced through rehabilitation. The decision for rehabilitation is based on several factors: type and severity of neurologic deficits, cognitive status, physical endurance, and preferences of patient and family. Implementation requires identification of learning patterns, sensitivity to the patient's responses, and establishment of realistic goals. Systematic assessment of impairments and disability is valuable for describing the impact of the stroke, monitoring recovery, evaluating response to specific interventions, and determining their long-term benefits. Because of the range of potential impairments, it is important to use a battery of assessment measures and to incorporate specific measures during each stage of recovery. In addition to assessments for neurologic disabilities, assessments for psychosocial conditions are necessary, as depression and dysphoria occur commonly and affect the rehabilitation and recovery of stroke patients. Their influence on physical function is currently being debated in the medical literature. The social context in which a stroke patient recovers also has profound effects on the success of the recovery process. Such factors as the amount of social support, income level, race, and life satisfaction affect the patient's rehabilitation process and adjustment. Standardization of assessment measures and a better understanding of the psychosocial factors that influence rehabilitation are necessary for helping stroke patients achieve an optimum functional quality of life.

The effects of specific medical conditions on the functional limitations of elders in the Framingham Study.

OBJECTIVES: The purpose of this study was to identify associations between specific medical conditions in the elderly and limitations in functional tasks; to compare risks of disability across medical conditions, controlling for age, sex, and comorbidity; and to determine the proportion of disability attributable to each condition. METHODS: The subjects were 709 noninstitutionalized men and 1060 women of the Framingham Study cohort (mean age 73.7 +/- 6.3 years). Ten medical conditions were identified for study: knee osteoarthritis, hip fracture, diabetes, stroke, heart disease, intermittent claudication, congestive heart failure, chronic obstructive pulmonary disease, depressive symptomatology, and cognitive impairment. Adjusted odds ratios were calculated for dependence on human assistance in seven functional activities. RESULTS: Stroke was significantly associated with functional limitations in all seven tasks; depressive symptomatology and hip fracture were associated with limitations in five tasks; and knee osteoarthritis, heart disease, congestive heart failure, and chronic obstructive pulmonary disease, were associated with limitations in four tasks each. CONCLUSIONS: In general, stroke, depressive symptomatology, hip fracture, knee osteoarthritis, and heart disease account for more physical disability in noninstitutionalized elderly men and women than other diseases.

Functional limitations and disability among elders in the Framingham Study.

BACKGROUND: The measurement of physical disability as an indication of the impact of disease is commonly seen in research. However, these measures often do not clearly differentiate between functional limitations and daily performance of an activity. METHODS: We measured the differences between self-reported disability and observed functional limitations in six activities of daily living tasks among community-dwelling elders. The value of functional limitations vs disability measures in determining risk factors for disablement was ascertained. RESULTS: Systematic differences were found among the 1453 participants. At least 89% of the time when a difference was identified, the subjects ranked disability greater than the functional limitations observed. For those who were cognitively impaired, discrepancies occurred up to 11% of the time. In determining risk factors for disablement, we found that neurological impairments were associated with both functional limitations and disability, while sociocultural factors were associated with disability only. CONCLUSIONS: Our findings suggest that physical functional limitations and disability in the elderly are two distinct concepts and that the measure of choice should be determined by research objectives and the type of population being studied.