Showing papers by "Peter W.F. Wilson published in 2001"

Validation of the Framingham coronary heart disease prediction scores: results of a multiple ethnic groups investigation.

Abstract: Context The Framingham Heart Study produced sex-specific coronary heart disease (CHD) prediction functions for assessing risk of developing incident CHD in a white middle-class population. Concern exists regarding whether these functions can be generalized to other populations. Objective To test the validity and transportability of the Framingham CHD prediction functions per a National Heart, Lung, and Blood Institute workshop organized for this purpose. Design, Setting, and Subjects Sex-specific CHD functions were derived from Framingham data for prediction of coronary death and myocardial infarction. These functions were applied to 6 prospectively studied, ethnically diverse cohorts (n = 23 424), including whites, blacks, Native Americans, Japanese American men, and Hispanic men: the Atherosclerosis Risk in Communities Study (1987-1988), Physicians' Health Study (1982), Honolulu Heart Program (1980-1982), Puerto Rico Heart Health Program (1965-1968), Strong Heart Study (1989-1991), and Cardiovascular Health Study (1989-1990). Main Outcome Measures The performance, or ability to accurately predict CHD risk, of the Framingham functions compared with the performance of risk functions developed specifically from the individual cohorts' data. Comparisons included evaluation of the equality of relative risks for standard CHD risk factors, discrimination, and calibration. Results For white men and women and for black men and women the Framingham functions performed reasonably well for prediction of CHD events within 5 years of follow-up. Among Japanese American and Hispanic men and Native American women, the Framingham functions systematically overestimated the risk of 5-year CHD events. After recalibration, taking into account different prevalences of risk factors and underlying rates of developing CHD, the Framingham functions worked well in these populations. Conclusions The sex-specific Framingham CHD prediction functions perform well among whites and blacks in different settings and can be applied to other ethnic groups after recalibration for differing prevalences of risk factors and underlying rates of CHD events.

Plasma Concentration of C-Reactive Protein and Risk of Ischemic Stroke and Transient Ischemic Attack: The Framingham Study

Abstract: 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 ris...

Metabolic Abnormalities and Cardiovascular Disease Risk Factors in Adults with Human Immunodeficiency Virus Infection and Lipodystrophy

Abstract: We evaluated metabolic and clinical features of 71 HIV-infected patients with lipodystrophy by comparing them with 213 healthy control subjects, matched for age and body mass index, from the Framingham Offspring Study. Thirty HIV-infected patients without fat redistribution were compared separately with 90 matched control subjects from the Framingham Offspring Study. Fasting glucose, insulin, and lipid levels; glucose and insulin response to standard oral glucose challenge; and anthropometric measurements were determined. HIV-infected patients with lipodystrophy demonstrated significantly increased waist-to-hip ratios, fasting insulin levels, and diastolic blood pressure compared with controls. Patients with lipodystrophy were more likely to have impaired glucose tolerance, diabetes, hypertriglyceridemia, and reduced levels of high-density lipoprotein (HDL) cholesterol than were controls. With the exception of HDL cholesterol level, these risk factors for cardiovascular disease (CVD) were markedly attenuated in patients without lipodystrophy and were not significantly different in comparison with controls. These data demonstrate a metabolic syndrome characterized by profound insulin resistance and hyperlipidemia. CVD risk factors are markedly elevated in HIV-infected patients with fat redistribution.

Abdominal Aortic Calcific Deposits Are an Important Predictor of Vascular Morbidity and Mortality

Abstract: Background—The impact of abdominal arterial calcific deposits on the prediction of cardiovascular disease (CVD) over a long follow-up interval deserves greater scrutiny. Methods and Results—Lateral lumbar radiographs were studied as a predictor of incident coronary heart disease (CHD), CVD, and CVD mortality in 1049 men and 1466 women (mean age, 61 years) who were followed from 1967 to 1989. Anterior and posterior wall calcific deposits in the aorta at the level of the first through fourth lumbar vertebrae were graded according to increasing severity using a previously validated rating scale for abdominal aortic calcium (AAC) that ranges from 0 to 24 points. There were 454 cases of CHD, 709 cases of CVD, and 365 CVD deaths. Proportional hazards logistic regression was used to test for associations between AAC and later events after adjustment for age, cigarette use, diabetes mellitus, systolic blood pressure, left ventricular hypertrophy, body mass index, cholesterol, and HDL cholesterol. In comparisons w...

Fasting Plasma Homocysteine Levels in the Insulin Resistance Syndrome: The Framingham Offspring Study

Abstract: OBJECTIVE —Insulin resistance, associated metabolic abnormalities, and elevated homocysteine levels are risk factors for cardiovascular disease (CVD). We examined relationships between homocysteine levels and features of insulin resistance syndrome (IRS). RESEARCH DESIGN AND METHODS —We measured clinical characteristics, plasma levels of fasting homocysteine, folate, B vitamins, creatinine, and fasting and 2-h insulin and glucose levels after a 75-g oral glucose tolerance test in 2,214 subjects without CVD at the fifth examination (1991–1995) of the Framingham Offspring Study. After excluding 203 subjects with diabetes, the remaining 2,011 subjects were categorized as having none, one, two, or all three of the phenotypes of IRS: impaired glucose tolerance, hypertension, and/or a central metabolic syndrome (two or more traits: obesity, dyslipidemia, or hyperinsulinemia). In addition, in 1,592 subjects attending the sixth examination (1995–1998), we measured the urine albumin/creatinine ratio (UACR). Age-, sex-, creatinine-, vitamin-, and UACR-adjusted mean homocysteine levels or proportions with homocysteine >14 μmol/l in each phenotypic category and differences between categories were assessed with regression models. RESULTS —The mean age of the subjects was 54 years (range 28–82); 55% were women, 12.3% had hyperinsulinemia, and 15.9% had two or more of the IRS phenotypes. Adjusted mean homocysteine levels were higher comparing those with hyperinsulinemia (9.8 μmol/l) and those without (9.4 μmol/l, P = 0.04) and were higher among subjects with two or more IRS phenotypes (9.9 μmol/l) compared with those with 1 or no phenotype (9.3 μmol/l, P = 0.003). Mean UACR levels were also higher among subjects with two or more IRS phenotypes (7.2 mg/g) compared with those with 1 or no phenotype (5.5 mg/g, P = 0.007). CONCLUSIONS —Hyperhomocysteinemia and abnormal urinary albumin excretion are both associated with hyperinsulinemia and may partially account for increased risk of CVD associated with insulin resistance. Because hyperhomocysteinemia and microalbuminuria also reflect endothelial injury, these observations also support the hypothesis that endothelial dysfunction is associated with expression of the IRS.

Intake of Dietary Phytoestrogens Is Low in Postmenopausal Women in the United States: The Framingham Study

Abstract: Many plants that are consumed contain phytoestrogens. Only a few published studies have examined the dietary intake of phytoestrogens in the general Western population. The potentially positive health effects of phytoestrogens might be of relevance to postmenopausal women. The aim of the present study was to estimate the intake of dietary isoflavones, coumestans and lignans by healthy Western postmenopausal women. For this purpose, we studied 964 postmenopausal, Caucasian women who participated in the Framingham Offspring Study and completed the Willett food-frequency questionnaire (FFQ). By searching the medical and agricultural literature and contacting experts, we identified food sources of phytoestrogens. The concentrations of the different isoflavones, coumestrol and lignans in each food in the FFQ were scored in seven categories and multiplied by the serving size of the food and the frequency of its consumption. The estimated daily median intake of the isoflavone daidzein was 39 microg (24-57 microg); of genistein, 70 microg (28-120 microg); of formononetin, 31 microg (13-44 microg); and of biochanin A, 6 microg (2-11 microg). Median total intake of isoflavones was 154 microg (99-235 microg). The main sources of isoflavones were beans and peas. The estimated daily intake of coumestans was 0.6 microg (0.2-1.7 microg), with broccoli as the main source. The estimated daily median intake of matairesinol was 19 microg (12-28 microg) and of secoisolariciresinol 560 microg (399-778 microg). The median total intake of lignans was 578 microg (416-796 microg). The main source of the lignans was fruits. The daily dietary intake of phytoestrogens in healthy postmenopausal Caucasian women in the United States is <1 mg.

Low Circulating Vitamin B6 Is Associated With Elevation of the Inflammation Marker C-Reactive Protein Independently of Plasma Homocysteine Levels

Abstract: Background—Lower vitamin B6 concentrations are reported to confer an increased and independent risk for cardiovascular disease (CVD). The mechanism underlying this relationship, however, remains to be defined. Other diseases, such as rheumatoid arthritis, are associated with reduced vitamin B6 levels. Despite a clear distinction in pathophysiology, inflammatory reaction may be the major link between these diseases. We hypothesized a relationship between pyridoxal 5′-phosphate (PLP), the active form of vitamin B6, and the marker of inflammation C-reactive protein (CRP). We also evaluated whether total plasma homocysteine (tHcy), a well-defined risk factor for CVD and a major determinant of plasma PLP levels, had a possible role as a mediator of this hypothesized relationship. Methods and Results—Data from 891 participants from the population-based Framingham Heart Study cohort were analyzed. Subjects were divided into 2 groups according to normal or elevated CRP values: group 1, CRP <6 mg/L; group 2, CRP ≥...

Cardiovascular Risk Assessment Based on US Cohort Studies Findings From a National Heart, Lung, and Blood Institute Workshop

Abstract: This report was derived from a workshop on cardiovascular risk assessment sponsored by the National Heart, Lung, and Blood Institute, which addressed whether risk equations developed in the Framingham Heart Study (FHS) for predicting new-onset coronary heart disease (CHD) apply to diverse population groups. Preparation for the workshop included a reanalysis and comparison of prospective studies in several different populations in which risk factors were related to cardiovascular outcomes. Some studies included fatal and nonfatal CHD end points, whereas others contained only CHD mortality. Extensive collaboration provided as much uniformity as possible with respect to both risk factors and CHD end points. The FHS has led in defining the quantitative impact of risk factors.1 Many potential risk factors were measured and related to cardiovascular outcomes. Several risk factors proved to be strong, largely independent predictors of cardiovascular disease (CVD). These factors—advancing age, cigarette smoking, blood pressure (particularly systolic), cholesterol in total serum and HDL, and diabetes—served as the basis for the development of risk prediction equations.1 If FHS risk estimates are to be widely used, they must apply widely in the US population. To document their transportability, they must be compared with prospective studies in other populations. Although the FHS is the longest running prospective study, there are other major studies. The cardiovascular end points of these other studies have varied. Some include cardiovascular morbidity and mortality; others have only cardiovascular mortality. Among the end points, CHD is the most extensively reported; for this reason, CHD was the primary focus of the workshop. ### Multivariate Relative Risk Comparisons In preparation for the workshop, multivariate regression coefficients for each risk factor were compared in different populations with those of the FHS. Adjusted relative risk estimates make it possible to determine whether each independent risk factor confers a similar or different relative risk among different …

Folic Acid Fortification Increases Red Blood Cell Folate Concentrations in the Framingham Study

Abstract: In 1996 the Food and Drug Administration (FDA) issued a regulation to take effect in January 1998 that all enriched cereal grain products include 140 microg of folic acid/100 g. The present cross-sectional study was undertaken to assess the effect of this fortification on RBC folate concentrations in the Framingham Offspring Cohort. Among those who did not take B-vitamin supplements, we compared RBC folate in 561 individuals who were examined before implementation of the FDA mandatory folic acid fortification (not exposed) vs. 354 individuals who were examined after implementation of fortification (exposed). We calculated the prevalence of deficient ( 200 microg/L, 453.2 nmol/L) RBC folate concentrations in both groups. Those exposed to folic acid fortification had a mean RBC folate of 450.0 microg/L (1019.7 nmol/L), a value 38% higher than the mean RBC folate of 325.3 microg/L (737.1 nmol/L) in those who were not exposed to fortification (P < 0.001). The prevalence of individuals with deficient RBC folate was 4.9% in the group not exposed to fortification compared with 1.9% in the group exposed to fortification (P < 0.02), and the prevalence of individuals with acceptable RBC folate was 87.0% in the group not exposed to fortification compared with 96.1% in the group exposed to fortification (P < 0.001). Similar results were seen in individuals who used supplements containing B-vitamins. The results of this study showed that in this cohort, the introduction of folic acid fortification significantly improved folate nutritional status measured as RBC folate.

Evaluation of dietary quality in relationship to nutritional and lifestyle factors in elderly people of the US Framingham Heart Study and the European SENECA study.

Abstract: Evaluation of dietary quality in relationship to nutritional and lifestyle factors in elderly people of the US Framingham Heart Study and the European SENECA study

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

Abstract: 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.

Postmenopausal estrogen use, type of menopause, and lens opacities: the Framingham studies.

Abstract: Background Previous studies of estrogen replacement therapy and lens opacities have not reported consistent findings. Objective To investigate whether postmenopausal estrogen use is associated with the occurrence of age-related lens opacities (nuclear, cortical, and posterior subcapsular). Methods Surviving members of the original cohort of the Framingham Heart Study who also participated in the Framingham Eye Study (1986-1989) were examined for the absence or presence of lens opacities. Data from the Framingham Heart Study, including information on menopausal status (collected biennially from approximately 1948) and use of estrogen replacement therapy (collected biennially from approximately 1960) were used to examine associations between lens opacities and duration of postmenopausal estrogen use, type of menopause, and age at menopause. Five hundred twenty-nine women, aged 66 to 93 years, were included. Multivariable-adjusted odds ratios of specific types of lens opacities were calculated for (1) duration of estrogen use (never and 1-2, 3-9, and ≥10 years), (2) surgical vs natural menopause, and (3) age at menopause. Results Longer duration of postmenopausal estrogen therapy was inversely associated with the presence of nuclear lens opacities in an adjusted model. Women who had taken estrogen for 10 years or longer had a 60% reduction in risk compared with nonusers (odds ratio, 0.4; 95% confidence interval, 0.2-1.01). Longer duration of estrogen use was associated with fewer posterior subcapsular opacities at a borderline level of significance. No association was noted for cortical opacities. The risk of posterior subcapsular opacities was significantly increased for women who had undergone surgical menopause compared with women with natural menopause (odds ratio, 2.2; 95% confidence interval, 1.1-4.3). No association was noted for lens opacities and age at menopause. Conclusion Data from our study and other studies suggest that a reduction in the risk of lens opacities may be an additional benefit of postmenopausal estrogen use.

Family Breast Cancer History and Mammography: Framingham Offspring Study

Abstract: The authors examined mammography use according to family cancer history and identified predictors of recent use (

Applicability of Cholesterol-Lowering Primary Prevention Trials to a General Population: The Framingham Heart Study

Abstract: Background Four large trials have shown cholesterol-reduction therapy to be effective for primary prevention of coronary heart disease (CHD). Methods To determine the generalizability of these trials to a community-based sample, we compared the total cholesterol and high-density lipoprotein cholesterol (HDL-C) distributions of patients in the 4 trials with those of Framingham Heart Study subjects. Lipid profiles that have not been studied were identified. Twelve-year rates of incident CHD were compared between subjects who met eligibility criteria and those who did not. Results The Framingham sample included 2498 men and 2870 women aged 30 to 74 years. Among Framingham men, 23.4% to 42.0% met eligibility criteria for each of the 4 trials based on their lipid levels; 60.2% met eligibility criteria for at least 1 trial. For the 1 trial that included women, 20.2% of Framingham women met eligibility criteria. In general, subjects with desirable total cholesterol levels and lower HDL-C levels and subjects with average total cholesterol levels and average to higher HDL-C levels have not been included in these trials. Among subjects who developed incident CHD during follow-up, 25.1% of men and 66.2% of women would not have been eligible for any trial. Most ineligible subjects who developed CHD had isolated hypertriglyceridemia (>2.25 mmol/L [>200 mg/dL]). Conclusions In our sample, 40% of men and 80% of women had lipid profiles that have not been studied in large trials to date. We observed a large number of CHD events in "ineligible" subjects in whom hypertriglyceridemia was common. Further studies are needed to define the role of lipid-lowering therapy vs other strategies for primary prevention in the general population.

Association of the Ala54-Thr polymorphism in the intestinal fatty acid-binding protein with 2-h postchallenge insulin levels in the Framingham Offspring Study.

Abstract: OBJECTIVE —To investigate the association of variants of the intestinal fatty acid–binding protein gene (FABP2) with fasting and postchallenge glucose and insulin levels, HbA 1c , and prevalence of type 2 diabetes in a separate sample of men and women. RESEARCH DESIGN AND METHODS —Subjects were participants in the Framingham Offspring Study, a long-term community-based prospective observational study of risk factors for cardiovascular disease. The study sample consisted of 762 men and 922 women. RESULTS —In women, carriers of the thr54 allele had significantly higher 2-h postchallenge insulin levels than noncarriers (104.4 ± 73.0 vs. 93.4 ± 61.5 μU/ml; P = 0.0139). This relationship remained significant after adjustment for familial relationship, age, BMI, triglycerides, APOE genotype, smoking, alcohol intake, the use of β-blockers, menopausal status, and estrogen therapy. No such significant association was observed in men. In both men and women, there were no statistical associations between the FABP2 polymorphism and BMI, fasting glucose, fasting insulin, 2-h postchallenge glucose levels, HbA 1c , and prevalence of type 2 diabetes. CONCLUSIONS —These results suggest that the FABP2 thr54 allele may have a minor contribution to the insulin resistance syndrome in a white general population.

Dyslipidaemia in Clinical Practice

Abstract: 1 Pathophysiology of Plasma Lipids 2 Dyslipidaemia as a Risk Factor for Cardiovascular Disease 3 Dietary and Lifestyle Factors in Dyslipidaemia 4 Screening for Dyslipidaemia 5 Clinical Assessment of Dyslipidaemia 6 Guidelines for the Management of Dyslipidaemia 7 Management Issues in Primary Care 8 Pharmacological Management of Dyslipidaemia

Plasma C-Reactive Protein, Systolic Hypertension and Risk of Ischemic Stroke and TIA: The Framingham Study

Abstract: 83 Background: The role of plasma C-reactive protein (CRP) as marker of cerebrovascular risk is currently under investigation. We evaluated relative risk of developing first ischemic stroke and TIA among the patients with elevated systolic blood pressure (SBP) and/or elevated plasma CRP levels versus those patients with unelevated SBP and unelevated CRP. Methods: We studied 591 men and 868 women of the original Framingham Study cohort who were free of stroke and TIA at the time of their 1980–1982 clinic exam. Sex-specific Cox proportional hazards regressions were used to quantify the risk of 14-year incidence of ischemic stroke/TIA associated with elevated SBP and CRP. Unadjusted models and models adjusted for age, smoking, total & HDL cholesterol, and diabetes were used. SBP and CRP were included in the Cox models as sex-specific quartiles. Risk ratios of first ischemic stroke/TIA for individuals with elevated (in the upper quartile) SBP (SBP+) and CRP (CRP+) were determined using the SBP-/CRP- individuals as a reference group. Similarly, simultaneous evaluation of the risk of first ischemic stroke/TIA was done for SBP+/CRP- and SBP-/CRP+ using the individuals in SBP-/CRP- as a reference group. Results: Relative to SBP-/CRP- men (incidence of first ischemic stroke/TIA of 36/328, or 11.0%), SBP+/CRP+ men (where incidence was 8/32, or 25.0%) had unadjusted risk ratio of 3.56 (p=0.001). This ratio was nearly twice that for SBP+/CRP- men (incidence=20/115, or 17.4%; RR=1.89, p=0.023). Relative to SBP-/CRP- women (incidence= 45/485, or 9.3%), the unadjusted risk ratio increased from 2.03 in SBP+/CRP- women (incidence=27/166, or 16.3%; p=0.001) to 3.44 in SBP+/CRP+ women (incidence=15/58, or 25.9%; p Conclusion: Having both CRP levels and systolic BP above the 75 th percentile for each of these parameters significantly increased risk of developing first ischemic stroke/TIA in both sexes.