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Biomedical subjects

Philip A Wolf

Publications and source records attributed to Philip A Wolf.

At least 19 recordsLinked to original sources
PubMed2007

Left ventricular mass, blood pressure, and lowered cognitive performance in the Framingham offspring.

The purpose of this study was to determine whether echocardiographic left ventricular mass is related to cognitive performance beyond casual blood pressure adjusting for the influence of other vascular risk factors. We used multivariable regression analyses to relate left ventricular mass assessed at a routine examination (1995-1998) to measures of cognitive ability obtained routinely (1998-2001) in 1673 Framingham Offspring Study participants (56% women; mean age: 57 years) free from stroke, transient ischemic attack, and dementia. We adjusted for the following covariates hierarchically: (1) age, education, sex, body weight, height, interval between left ventricular mass measurement and neuropsychological testing (basic model); (2) basic model+blood pressure+treatment for hypertension; and (3) basic model+blood pressure+treatment for hypertension+vascular risk factors and prevalent cardiovascular disease. For the basic model, left ventricular mass was inversely associated with abstract reasoning (similarities), visual-spatial memory and organization, and verbal memory. For the basic model+blood pressure+treatment for hypertension, left ventricular mass was inversely associated with similarities and visual-spatial memory and organization. For the basic+blood pressure+treatment for hypertension+risk factors+cardiovascular disease model, no significant associations were observed. Echocardiographic left ventricular mass is associated with cognitive performance beyond casual and time-averaged systolic blood pressure, but this association is attenuated and rendered nonsignificant with additional adjustment for cardiovascular risk factors and cardiovascular disease, thus suggesting that these variables play an important role in mediating the association between left ventricular mass and cognition.

Blood Pressure↗
PubMed2006

Trends in incidence, lifetime risk, severity, and 30-day mortality of stroke over the past 50 years.

CONTEXT: Prior estimates of long-term trends in the incidence and severity of stroke have varied; trends in lifetime risk have not been reported. OBJECTIVE: To determine long-term trends in the incidence, lifetime risk, severity, and 30-day mortality of clinical stroke. DESIGN, SETTING, AND PARTICIPANTS: Prospective evaluation of the community-based Framingham Study original and offspring cohorts. Participants were 9152 men and women free of prevalent stroke and undergoing follow-up for up to 50 years over 3 consecutive periods (1950-1977, 1978-1989, and 1990-2004), with biennial ascertainment of stroke risk factor data and active surveillance for incident clinical stroke and cause-specific mortality. MAIN OUTCOME MEASURES: Incidence (age-adjusted, sex-specific), severity, 30-day mortality, and mortality-adjusted 10-year and lifetime risk of stroke in each of the specified periods. RESULTS: There were 1030 incident clinical strokes (450 [44%] in men, 629 atherothrombotic brain infarctions [61%]) in 9152 persons 55 years or older over 174,917 person-years of follow-up. The age-adjusted incidence of first stroke per 1000 person-years in each of the 3 periods was 7.6, 6.2, and 5.3, respectively, in men (P = .02 for trend) and 6.2, 5.8, and 5.1 in women (P = .01 for trend). The lifetime risk at age 65 years decreased from 19.5% to 14.5% in men (P = .11) and from 18.0% to 16.1% in women (P = .61). Age-adjusted stroke severity did not vary across periods; however, 30-day mortality decreased significantly in men (from 23% to 14%; P = .01) but not significantly in women (from 21% to 20%; P = .32). CONCLUSIONS: In this cohort of men and women free of prevalent clinical stroke at initial examination, incidence of stroke has decreased over the past 50 years but the lifetime risk has not declined to the same degree, perhaps due to improved life expectancy. The results of this study suggest that improved control of risk factors has lowered stroke incidence but emphasize the need for continued primary prevention efforts.

Adult↗
PubMed2006

Depressive symptoms and risk of stroke: the Framingham Study.

BACKGROUND AND PURPOSE: Emerging evidence raises the possibility of an association between depression and stroke risk. This study sought to examine whether depressive symptoms are associated with an increased risk of cerebrovascular events in a community-based sample. METHODS: A prospective study was conducted on 4120 Framingham Heart Study participants aged 29 to 100 years with up to 8 years of follow-up. The Center for Epidemiologic Studies Depression Scale was used to measure depressive symptoms. Incident stroke and transient ischemic attack (TIA) events were assessed by uniform diagnostic criteria. The association between depressive symptoms and risk of stroke/TIA was analyzed with Cox proportional-hazards models, after adjusting for traditional stroke risk factors. RESULTS: In participants <65 years, the risk of developing stroke/TIA was 4.21 times greater (P= <0.001) in those with symptoms of depression. After adjusting for components of the Framingham Stroke Risk Profile (hazard ratio=3.43, 95% CI=1.60 to 7.36, P=0.002) and education (hazard ratio=4.89, 95% CI=2.19 to 10.95), similar results were obtained. In subjects aged 65 and older, depressive symptoms were not associated with an increased risk of stroke/TIA. Taking antidepressant medications did not alter the risk associated with depressive symptoms. CONCLUSIONS: In this community-based study, depressive symptoms were an independent risk factor for incident stroke/TIA in individuals <65 years. These data suggest that identification of depressive symptoms at younger ages may have an impact on the primary prevention of stroke.

Adult↗
PubMed2006

Longitudinal genetic analysis of executive function in elderly men.

The objective of this study was to characterize the relative contribution of genetic and environmental influences to individual differences in longitudinal performance and decline of executive function (EF) using a population-based prospective study of male, WWII veteran twins (NHLBI twin study). Three tests of EF were administered when the twins were 59-70 years old, with 9- and 13-year follow-up. APOE epsilon4 allele status was incorporated in the genetic models to determine its contribution to longitudinal genetic variability. Mean EF performance significantly worsened over time. EF performance was highly genetically correlated across repeat assessment. There were significant genetic influences on 9- and 13-year decline in digit symbol performance. For all tasks decline over the last 4-year follow-up was influenced by individual-specific environmental effects. Controlling for APOE epsilon4 allele presence did not appreciably change the magnitude of genetic effects. These results suggest that common genetic factors underlie longitudinal EF task performance. Genetic influences on EF decline, however, appear to be evident at longer time intervals between assessments.

Aged↗
PubMed2006

Variants at the APOA5 locus, association with carotid atherosclerosis, and modification by obesity: the Framingham Study.

Genetic variation at the apolipoprotein A5 gene (APOA5) is associated with increased triglyceride concentrations, a risk factor for atherosclerosis. Carotid intimal medial thickness (IMT) is a surrogate measure of atherosclerosis burden. We sought to determine the association of common APOA5 genetic variants with carotid IMT and stenosis. A total of 2,273 Framingham Offspring Study participants underwent carotid ultrasound and had data on at least one of the five APOA5 variants (-1131T>C, -3A>G, 56C>G, IVS3+476G >A, and 1259T>C). Although none of the individual variants was significantly associated with carotid measures, the haplotype defined by the presence of the rare allele of the 56C>G variant was associated with a higher common carotid artery (CCA) IMT compared with the wild-type haplotype (0.75 vs. 0.73 mm; P < 0.05). The rare allele of each of the -1131T >C, -3A>G, IVS3+476G>A, and 1259T>C variants and the haplotype defined by the presence of the rare alleles in these four variants were each significantly associated with CCA IMT in obese participants. These associations remained significant even after adjustment for triglycerides. APOA5 variants were associated with CCA IMT, particularly in obese participants. The mechanism of these associations and the effect modification by obesity are independent of fasting triglyceride levels.

Apolipoprotein A-V↗
PubMed2006

Prediction of lifetime risk for cardiovascular disease by risk factor burden at 50 years of age.

BACKGROUND: Lifetime risk for atherosclerotic cardiovascular disease (CVD) has not previously been estimated, and the effect of risk factor burden on lifetime risk is unknown. METHODS AND RESULTS: We included all Framingham Heart Study participants who were free of CVD (myocardial infarction, coronary insufficiency, angina, stroke, claudication) at 50 years of age. Lifetime risks to 95 years of age were estimated for men and women, with death free of CVD as a competing event. We followed up 3564 men and 4362 women for 111,777 person-years; 1757 had CVD events and 1641 died free of CVD. At 50 years of age, lifetime risks were 51.7% (95% CI, 49.3 to 54.2) for men and 39.2% (95% CI, 37.0 to 41.4) for women, with median survivals of 30 and 36 years, respectively. With more adverse levels of single risk factors, lifetime risks increased and median survivals decreased. Compared with participants with > or =2 major risk factors, those with optimal levels had substantially lower lifetime risks (5.2% versus 68.9% in men, 8.2% versus 50.2% in women) and markedly longer median survivals (>39 versus 28 years in men, >39 versus 31 years in women). CONCLUSIONS: The absence of established risk factors at 50 years of age is associated with very low lifetime risk for CVD and markedly longer survival. These results should promote efforts aimed at preventing development of risk factors in young individuals. Given the high lifetime risks and lower survival in those with intermediate or high risk factor burden at 50 years of age, these data may be useful in communicating risks and supporting intensive preventive therapy.

Age Factors↗
PubMed2006

Association between well-characterized lipoprotein-related genetic variants and carotid intimal medial thickness and stenosis: The Framingham Heart Study.

OBJECTIVE: To determine the association of well-characterized lipoprotein-related genetic variants with carotid intimal medial thickness (IMT) and stenosis. METHODS: 3380 men and women from the Framingham Offspring Study underwent carotid ultrasound to determine carotid IMT and stenosis>/=25%. We genotyped 12 variants in 10 lipoprotein-related genes known to be associated with significant differences in lipoprotein levels. RESULTS: For most of the variants, there was no association with carotid IMT. In multivariable, sex-specific analyses, the rare allele of the cholesterol ester transfer protein (CETP) TaqIB variant was associated with lower ICA IMT in men. Hypertension was associated with higher ICA IMT only in male carriers of the rare allele of the APOCIII Sst-1 variant (p for the interaction=0.041). In analyses of carotid stenosis in male, carriers of the lipoprotein lipase (LPL) N291S rare variant showed a higher risk of carotid stenosis (OR=2.59, 95% confidence interval: 1.11-6.02, p=0.028) compared to NN genotype. CONCLUSIONS: While there is no evidence for a significant association of several common lipoprotein-related genetic variants with carotid IMT, our results are consistent with the previously reported role of CETP and LPL genetic variants in cardiovascular risk and the possible modulation of the association between hypertension and carotid IMT by APOCIII Sst-1 variant.

Adolescent↗
PubMed2006

Metabolic syndrome compared with type 2 diabetes mellitus as a risk factor for stroke: the Framingham Offspring Study.

BACKGROUND: Metabolic syndrome (MetS) has been recognized as a prediabetic constellation of symptoms and an independent risk factor for cardiovascular disease. METHODS: To evaluate the age-adjusted risk of stroke and population-attributable risk associated with MetS and compare with those of overt type 2 diabetes mellitus (hereinafter, "diabetes"), we determined the prevalence of MetS alone, diabetes alone, and both in 2097 subjects in the Framingham Offspring Study, aged 50 to 81 years and free of stroke. Age-adjusted risk ratios, 10-year incidence, and population-attributable risks of stroke were estimated for men and women with MetS alone, diabetes alone, and both. RESULTS: Criteria for MetS were met in 30.3% of men and 24.7% of women. Twenty-four percent of men had MetS alone; 7% had diabetes alone; and 6% had both. Twenty percent of women had MetS alone; 3% had diabetes alone; and 5% had both. Over 14 years of follow-up, 75 men and 55 women developed a first stroke; all but 4 events were ischemic. Relative risk (RR) of stroke in persons with both diabetes and MetS (RR, 3.28; confidence interval [CI], 1.82-5.92) was higher than that for either condition alone (MetS alone: RR, 2.10; CI, 1.37-3.22; diabetes alone: RR, 2.47; CI, 1.31-4.65). The population-attributable risk, owing to its greater prevalence, was greater for MetS alone than for diabetes alone (19% vs 7%), particularly in women (27% vs 5%). CONCLUSIONS: Metabolic syndrome is more prevalent than diabetes and a significant independent risk factor for stroke in people without diabetes. Prevention and control of MetS and its components are likely to reduce stroke incidence.

Age Distribution↗
PubMed2006

The lifetime risk of stroke: estimates from the Framingham Study.

BACKGROUND AND PURPOSE: The lifetime risk (LTR) of stroke has not been reported for the United States population; such data would assist public education and health planning. METHODS: Framingham Original cohort participants (n=4897) who were stroke- and dementia-free at 55 years of age were followed biennially for up to 51 years (115 146 person years). We estimated the sex-specific 10-, 20-, and 30-year risks and LTR of developing a stroke by baseline age and blood pressure (BP) and compared it with the risk of developing Alzheimer disease (AD). RESULTS: A total of 875 participants (522 women) developed a first-ever stroke; 749 (448 women) had an ischemic stroke. LTR of stroke was high and remained similar at ages 55, 65, and 75 years, approximating 1 in 5 for women and 1 in 6 for men. Participants with a normal BP (<120/80 mm Hg) had approximately half the LTR of stroke compared with those with high BP (> or =140/90 mm Hg). The LTR of AD at age 65 (292 participants; 211 women) approximated 1 in 5 for women and 1 in 10 for men. The LTR of developing either stroke or dementia approximated 1 in 3 in both sexes. CONCLUSIONS: The LTR of stroke in middle-aged adults is 1 in 6 or more, which is equal to or greater than the LTR of AD. Women had a higher risk because of longer life expectancy. BP is a significant determinant of the LTR of stroke, and promotion of normal BP levels in the community might be expected to substantially reduce this risk.

Age Factors↗
PubMed2006

Plasma phosphatidylcholine docosahexaenoic acid content and risk of dementia and Alzheimer disease: the Framingham Heart Study.

BACKGROUND: Docosahexaenoic acid (DHA) is an abundant fatty acid in the brain. In the diet, DHA is found mostly in fatty fish. The content of DHA has been shown to be decreased in the brain and plasma of patients with dementia. OBJECTIVE: To determine whether plasma phosphatidylcholine (PC) DHA content is associated with the risk of developing dementia. DESIGN, SETTING, AND PARTICIPANTS: A prospective follow-up study in 899 men and women who were free of dementia at baseline, had a median age of 76.0 years, and were followed up for a mean of 9.1 years for the development of all-cause dementia and Alzheimer disease. MAIN OUTCOME MEASURES: Plasma PC fatty acid levels were measured at baseline. Cox proportional regression analysis was used to assess relative risks of all-cause dementia and Alzheimer disease according to baseline plasma levels. RESULTS: Ninety-nine new cases of dementia (including 71 of Alzheimer disease) occurred during the follow-up. After adjustment for age, sex, apolipoprotein E epsilon4 allele, plasma homocysteine concentration, and education level, subjects in the upper quartile of baseline plasma PC DHA levels, compared with subjects in the lower 3 quartiles, had a relative risk of 0.53 of developing all-cause dementia (95% confidence interval, 0.29-0.97; P=.04) and 0.61 of developing Alzheimer disease (95% confidence interval, 0.31-1.18; P=.14). Subjects in the upper quartile of plasma PC DHA levels had a mean DHA intake of 0.18 g/d and a mean fish intake of 3.0 servings per week (P<.001) in a subset of 488 participants. We found no other significant associations. CONCLUSION: The top quartile of plasma PC DHA level was associated with a significant 47% reduction in the risk of developing all-cause dementia in the Framingham Heart Study.

Aged↗
PubMed2006

Diabetes mellitus and risk of developing Alzheimer disease: results from the Framingham Study.

BACKGROUND: Diabetes mellitus (DM) could increase the risk of Alzheimer disease (AD) through several biologically plausible pathways, but the relationship between DM and the development of AD remains uncertain. OBJECTIVE: To compare the risk of developing AD in subjects with and without DM. DESIGN: Prospective community-based cohort study. PARTICIPANTS: Framingham Study Original cohort participants who were dementia free and attended the 16th biennial examination (n = 2210 persons, 1325 women; mean age, 70 years). MAIN OUTCOME MEASURES: Relative risk of incident AD (criteria from the National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association) associated with baseline DM (casual plasma glucose >or=200 mg/dL [>or=11.1 mmol/L] or use of insulin or a hypoglycemic drug) in overall group and within subgroups defined by apolipoprotein E genotype and plasma homocysteine levels; models were adjusted for age, sex, and cardiovascular risk factors. RESULTS: At baseline, 202 participants (9.1%) had DM. During the follow-up period (mean, 12.7 years; range, 1-20 years), 17 of 202 persons with DM (8.4%) and 220 of 2008 persons without DM (11.0%) developed AD, yielding a relative risk of 1.15 (95% confidence interval, 0.65-2.05). Among subjects without an apolipoprotein E epsilon4 allele or elevated plasma homocysteine levels, 44 of 684 persons (6.4%) developed AD; relative risk for AD comparing diabetic patients with nondiabetic patients was 2.98 (95% confidence interval, 1.06-8.39; P = .03). The effect was strongest in persons aged 75 years or older with a relative risk of 4.77 (95% confidence interval, 1.28-17.72; P = .02). CONCLUSION: Diabetes mellitus did not increase the risk of incident AD in the Framingham cohort overall; however, DM may be a risk factor for AD in the absence of other known major AD risk factors.

Aged↗
PubMed2006

Association of white matter hyperintensity volume with decreased cognitive functioning: the Framingham Heart Study.

OBJECTIVE: To examine the relationship between white matter hyperintensity (WMH) volume on magnetic resonance images and cognitive tests in a large, population-based sample. METHODS: Quantitative magnetic resonance imaging and neuropsychological evaluations were performed in 1820 dementia- and stroke-free participants from the Framingham Offspring Cohort. The WMH volume relative to total cranial volume was computed; WMH volumes more than 1 SD above the age-predicted mean were defined as large. Adjusting for age, sex, education, height, and Framingham Stroke Risk Profile, we examined the relationship between WMH and 3 cognitive factors derived from a neuropsychological test battery (verbal memory, visuospatial memory and organization, and visual scanning and motor speed) and 3 individual measures of new learning, abstract reasoning, and naming. RESULTS: Compared with those with no or little WMH volume, participants with large WMH volume performed worse on the cognitive factors of visuospatial memory and organization (P = .04) and visual scanning and motor speed (P = .01), as well as on new learning (P = .04), but not on verbal memory (P = .52). CONCLUSIONS: In this younger community-based population of nondemented individuals, those with large WMH volume, as compared with those with less or no WMH volumes, performed significantly worse in cognitive domains generally associated with frontal lobe systems and, to a lesser extent, the medial temporal area. Further study will clarify whether large WMH volume and associated cognitive impairment lead to future risk of stroke or dementia.

Age Factors↗
PubMed2006

Peripheral and cerebral atherothrombosis and cardiovascular events in different vascular territories: insights from the Framingham Study.

Major risk factors for clinical atherosclerosis include dyslipidemia, hypertension, glucose intolerance, adiposity, cigarette smoking, hemostatic factors, inflammatory markers, and sedentary lifestyle. Sets of some of these and evidence of vascular damage such as left ventricular hypertrophy and atrial fibrillation are used to formulate multivariable risk profiles for peripheral artery disease and stroke. These global risk formulations facilitate office estimation of the risk of these disabling diseases, which often indicate diffuse systemic atherosclerosis. Because predisposing risk factors usually cluster, and the risk each imposes varies widely, global risk assessment is a necessity, especially now that average risk factor levels are recommended for treatment. Novel risk factors deserve attention, but the standard cardiovascular risk factors account for as much as 85% of the cardiovascular disease arising within the population. Further improvement in detection, evaluation, and control of the major risk factors by implementation of guidelines for primary and secondary prevention of stroke and peripheral artery disease is needed, particularly in the high-risk segment of the population.

Atherosclerosis↗
PubMed2006

Visual association pathology in preclinical Alzheimer disease.

The transition from normal aging to mild cognitive impairment to Alzheimer disease (AD) is often indistinct. Imaging studies suggest early changes in posterior brain regions, including posterior temporoparietal and occipital cortex, but pathologic studies show initial changes in the medial temporal lobe with progressive neocortical involvement as cognition deteriorates. We evaluated the regional distribution of AD pathology in 41 elderly brain donors from the Framingham Heart Study who were cognitively intact, mildly impaired, or demented on the basis of probable AD. We found that 52% of the cognitively intact subjects, and all subjects with mild cognitive impairment or dementia, had dense neurofibrillary tangles (NFTs), neuropil threads, and tau-immunoreactive neurites surrounding neuritic plaques (NPs) in visual association cortex Brodmann area 19. All cognitively intact subjects with area 19 NFTs also had dense core NP and beta amyloid (Abeta) angiopathy in area 19. Area 19 pathology was occasionally present in the absence of substantial pathology in the hippocampus or entorhinal cortex and was not correlated with medial temporal lobe pathology. Dense AD pathology in area 19 is present in some cognitively intact subjects with preclinical AD. The unique metabolic, connectional, and vascular features of this region may confer enhanced vulnerability to neurodegeneration.

Aged↗
PubMed2005

Genome-wide scan for white matter hyperintensity: the Framingham Heart Study.

BACKGROUND AND PURPOSE: White matter hyperintensity (WMH) volume is associated with aging and cerebrovascular disease and has been demonstrated to have a high heritability in the Framingham Heart Study as well as in other studies. We performed a genome-wide linkage analysis to identify chromosomal regions that may harbor genes influencing WMH in a family-based sample of the Framingham Heart Study. METHODS: Brain magnetic resonance scans were performed, and WMH and total cranial volume (TCV) were quantified as previously described on 2259 cohort and offspring participants. The outcome used for linkage analysis was an age specific (within 10-year age groups) z-score for the natural logarithm of the ratio of WMH to TCV. This z-score was based on 2230 individuals after excluding 26 participants with neurological conditions other than stroke and 3 individuals whose ages were out of range. Variance component linkage analysis included 747 individuals (mean age=62.16+/-12.43 years) with both magnetic resonance measure and genotype information in 237 families. Mean percent WMH to TCV was 0.098+/-0.175 with a range of 0.00025% to 1.37% in the linkage analysis subjects. RESULTS: A maximum multipoint logarithm of the odds (LOD) score=3.69, which indicates significant evidence of linkage, was observed at 4 cM on chromosome 4. A suggestive peak with LOD=1.78 was observed at 95 cM on chromosome 17. CONCLUSIONS: We have significant evidence that a gene influencing WMH volume is located on chromosome 4 of the human genome.

Adult↗
PubMed2005

Obesity, diabetes and cognitive deficit: The Framingham Heart Study.

OBJECTIVE: To determine the independent effects of obesity on cognitive performance and to examine interactions between obesity and non-insulin dependent diabetes mellitus (NIDDM). METHODS: Using a prospective design, male (n=551) and female (n=872) participants of the Framingham Heart Study were classified as obese (yes/no), diabetic (yes/no), and the number of diabetes-years was determined by data collected over an 18-year surveillance period. All subjects were free from dementia, stroke, and clinically diagnosed cardiovascular disease up to the time of cognitive testing. Statistical models were adjusted for age, education, occupation, native language, and cardiovascular disease risk factors. Body mass index status (non-obese or obese) and NIDDM status (diabetic/non-diabetic) were related to cognitive performance on multiple cognitive measures. RESULTS: Adverse effects of obesity on cognitive performance were observed for men only. Diabetes-years related to poorer cognitive performance, but only when men and women were combined for analyses. Neither diabetes nor diabetes-years by obesity interactions were observed. CONCLUSIONS: The gender-specific results for obesity, but not for diabetes, suggests that the underlying mechanisms linking them to cognition may be different.

Aged↗
PubMed2005

Homocysteine and cognitive performance in the Framingham offspring study: age is important.

Plasma total homocysteine (tHcy) concentrations are associated with deficits in cognitive performance in persons free from dementia. The extent to which age modifies these associations is in need of further investigation in large, community-based, prospective studies combining the following elements: 1) multiple cognitive tests; 2) statistical adjustment for the role of the vitamin cofactors folate, vitamin B6, and vitamin B12; and 3) adjustment for the presence of risk factors for cardiovascular disease and stroke. Using data collected between 1991 and 2002, the authors investigated the associations between tHcy and multiple measures of cognitive performance in 2,096 dementia- and stroke-free participants of the Framingham Offspring Study, who were stratified into three age groups (40-49 years, 50-59 years, 60-82 years), after findings of statistically significant tHcy-by-age interactions for multiple cognitive measures. Regardless of statistical adjustment for age, sex, gender, the vitamin cofactors, and cardiovascular risk factors, statistically significant inverse associations between tHcy and multiple cognitive domains were observed for individuals aged 60 or more years; no such associations were observed for participants aged less than 60 years. Early preventive interventions may be important, because the inverse association between tHcy and cognitive performance is observed beyond middle age.

Adult↗