Biomedical subjects

Daniel Levy

Publications and source records attributed to Daniel Levy.

At least 73 records · Page 4Linked to original sources

PubMed2004

Warfarin and aspirin use and the predictors of major bleeding complications in atrial fibrillation (the Framingham Heart Study).

The Framingham Heart Study records of participants with atrial fibrillation (AF) during 1980 and 1994 were retrospectively reviewed to determine the prevalence of warfarin and aspirin use in AF. Anticoagulant use increased significantly in the 393 men and women (mean ages 72.5 and 79.0 years, respectively) who developed AF over the observation period: aspirin use increased from 14% to 39% in men and from 19% to 33% in women, and warfarin use increased from 10% to 39% in men and from 17% to 38% in women. There were no significant gender differences in anticoagulant use (p = 0.61), but participants using warfarin were younger. A total of 65 participants (17%) had major bleeding complications <or=5 years after initial AF. Age was not a significant predictor of bleeding.

Adult↗

PubMed2004

Survival associated with two sets of diagnostic criteria for congestive heart failure.

Congestive heart failure (CHF) definitions vary across epidemiologic studies. The Framingham Heart Study criteria include CHF signs and symptoms assessed by a physician panel. In the Cardiovascular Health Study, a committee of physicians adjudicated CHF diagnoses, confirmed by signs, symptoms, clinical tests, and/or medical therapy. The authors used data from the Cardiovascular Health Study, a population-based cohort study of 5,888 elderly US adults, to compare CHF incidence and survival patterns following onset of CHF as defined by Framingham and/or Cardiovascular Health Study criteria. They constructed an inception cohort of nonfatal, hospitalized CHF patients. Of 875 participants who had qualifying CHF hospitalizations between 1989 and 2000, 54% experienced a first CHF event that fulfilled both sets of diagnostic criteria (concordant), 31% fulfilled only the Framingham criteria (Framingham only), and 15% fulfilled only the Cardiovascular Health Study criteria (Cardiovascular Health Study only). No significant survival difference was found between the Framingham-only group (hazard ratio = 0.87, 95% confidence interval: 0.71, 1.07) or the Cardiovascular Health Study-only group (hazard ratio = 0.89, 95% confidence interval: 0.68, 1.15) and the concordant group (referent). Compared with Cardiovascular Health Study central adjudication, Framingham criteria for CHF identified a larger group of participants with incident CHF, but all-cause mortality rates were similar across these diagnostic classifications.

Aged↗

PubMed2004

Usefulness of exercise testing in the prediction of coronary disease risk among asymptomatic persons as a function of the Framingham risk score.

BACKGROUND: The purpose of this study is to determine the usefulness of exercise treadmill testing (ETT) among asymptomatic persons in predicting coronary heart disease (CHD) events over and above the Framingham CHD risk score. METHODS AND RESULTS: Subjects included 3043 members of the Framingham Heart Study offspring cohort without CHD (1431 men and 1612 women; age, 45+/-9 years) who underwent ETT and were followed up for 18.2 years. The risk of developing CHD was evaluated relative to 3 exercise test variables: (1) ST-segment depression > or =1 mm, (2) failure to achieve target heart rate (THR) of 85% predicted maximum, and (3) exercise capacity. In multivariable analyses that adjusted for age and Framingham CHD risk score, among men, ST-segment depression (hazard ratio [HR], 1.88; 95% CI, 1.21 to 2.91) and failure to achieve THR (HR, 1.70; 95% CI, 1.18 to 2.45) predicted higher CHD risk, whereas a greater exercise capacity predicted lower CHD risk (HR per MET, 0.94; 95% CI, 0.89 to 0.99). Although similar HRs were seen in women, those results were not statistically significant. Among men with 10-year predicted risk > or =20%, failure to reach THR and ST-segment depression both more than doubled the risk of an event (HR, 2.66 and HR, 2.11, respectively), and each MET increment in exercise capacity reduced risk by 13% (HR, 0.87). CONCLUSIONS: Among asymptomatic men, ST-segment depression, failure to reach THR, and exercise capacity during ETT provided additional prognostic information in age- and Framingham risk score-adjusted models, particularly among those in the highest risk group (10-year predicted CHD risk of > or =20%). The evaluation of exercise test variables in women is limited, given our sample size and the few CHD events in women.

Adult↗

PubMed2004

Lifetime risk for development of atrial fibrillation: the Framingham Heart Study.

BACKGROUND: Atrial fibrillation (AF) is the most common cardiac dysrhythmia and a source of considerable morbidity and mortality, but lifetime risk for AF has not been estimated. METHODS AND RESULTS: We included all participants in the Framingham Heart Study who were free of AF at index ages of 40 years and older. We estimated lifetime risks for AF (including atrial flutter) to age 95 years, with death free of AF as a competing event. We followed 3999 men and 4726 women from 1968 to 1999 (176 166 person-years); 936 participants had development of AF and 2621 died without prior AF. At age 40 years, lifetime risks for AF were 26.0% (95% CI, 24.0% to 27.0%) for men and 23.0% (21.0% to 24.0%) for women. Lifetime risks did not change substantially with increasing index age despite decreasing remaining years of life because AF incidence rose rapidly with advancing age. At age 80 years, lifetime risks for AF were 22.7% (20.1% to 24.1%) in men and 21.6% (19.3% to 22.7%) in women. In further analyses, counting only those who had development of AF without prior or concurrent congestive heart failure or myocardial infarction, lifetime risks for AF were approximately 16%. CONCLUSIONS: Lifetime risks for development of AF are 1 in 4 for men and women 40 years of age and older. Lifetime risks for AF are high (1 in 6), even in the absence of antecedent congestive heart failure or myocardial infarction. These substantial lifetime risks underscore the major public health burden posed by AF and the need for further investigation into predisposing conditions, preventive strategies, and more effective therapies.

Adult↗

PubMed2004

Meta-analysis of genome-wide scans for hypertension and blood pressure in Caucasians shows evidence of susceptibility regions on chromosomes 2 and 3.

Individual genome-wide scans of blood pressure (BP) and hypertension (HT) have shown inconsistent results. The aim of this study was to investigate whether there was any consistent evidence of linkage across multiple studies with similar ethnicity. We applied the genome-search meta-analysis method (GSMA) to nine published genome-wide scans of BP (n = 5) and HT (n = 4) from Caucasian populations. For each study, the genome was divided into 120 bins and ranked according to the maximum evidence of linkage within each bin. The ranks were summed and averaged across studies and significance levels were estimated, on the basis of a distribution function of summed ranks or permutation tests without (PU) or with (PW) a study sample size weighting factor. Chromosome 3p14.1-q12.3 showed consistent evidence of linkage to HT (PU = 0.0001 and PW = 0.0001), diastolic BP (DBP) (PU = 0.007 and PW = 0.02), HT and DBP pooled (PU = 0.00002 and PW = 0.0001) and HT and systolic BP (SBP) pooled (PU = 0.0003 and PW = 0.0005). Chromosome 2p12-q22.1 showed evidence of linkage to HT (PU = 0.003 and PW = 0.009), DBP (PU = 0.05 and PW = NS), HT and DBP pooled (PU = 0.001 and PW = 0.004) and HT and SBP pooled (PU = 0.001 and P W = 0.005). The summed ranks of the HT analysis correlated significantly with those of the DBP (r = 0.20, P = 0.03) but not with those of the SBP. Both loci showed clustering of significant bins in the analysis of HT and DBP. We conclude that modest or non-significant linkage on chromosomes 3p14.1-q12.3 and 2p12-q22.1 in each individual study translates into genome-wide significant or highly suggestive linkages to HT and DBP in our GSMA analysis.

Blood Pressure↗

PubMed2004

Temporal trends in coronary heart disease mortality and sudden cardiac death from 1950 to 1999: the Framingham Heart Study.

BACKGROUND: Throughout the past 50 years, heart disease has been the leading cause of death in the United States. Although declines in coronary heart disease (CHD) mortality have been noted, there is still uncertainty about the magnitude of the decline and whether the trend is similar for sudden cardiac death (SCD). METHODS AND RESULTS: We examined temporal trends in SCD and nonsudden CHD death in the Framingham Heart Study original and offspring cohorts from 1950 to 1999. SCD was defined as a death attributed to CHD with preceding symptoms that lasted less than 1 hour; all deaths were adjudicated by a physician panel. Log-linear Poisson regression was used to estimate CHD mortality and SCD risk ratios (RRs); RRs were adjusted for age and gender. There were 811 CHD deaths: 453 nonsudden and 358 SCDs. Ninety-one (20%) of nonsudden CHD deaths and 173 (48%) of SCDs were in subjects free of antecedent CHD. From 1950-1969 to 1990-1999, overall CHD death rates decreased by 59% (95% CI 47% to 68%, P(trend)<0.001). Nonsudden CHD death decreased by 64% (95% CI 50% to 74%, P(trend)<0.001), and SCD rates decreased by 49% (95% CI 28% to 64%, P(trend)<0.001). These trends were seen in men and women, in subjects with and without a prior history of CHD, and in smokers and nonsmokers. CONCLUSIONS: The risks of SCD and nonsudden CHD mortality have decreased by 49% to 64% over the past 50 years. These trends were evident in subjects with and without heart disease, which suggests important contributions of primary and secondary prevention to the decreasing risk of CHD death and SCD.

Adult↗

PubMed2004

Local shear stress and brachial artery flow-mediated dilation: the Framingham Heart Study.

Endothelium-dependent flow-mediated dilation is a homeostatic response to short-term increases in local shear stress. Flow-mediated dilation of the brachial artery in response to postischemic reactive hyperemia is impaired in patients with cardiovascular disease risk factors and may reflect local endothelial dysfunction in the brachial artery. However, previous studies have largely neglected the effect of risk factors on evoked shear stress, which is the stimulus for dilation. We evaluated brachial artery percent dilation and evoked diastolic shear stress during reactive hyperemia using high-resolution ultrasound and Doppler in 2045 participants (1107 women, mean age 61 years) in the Framingham Offspring Study. In age- and sex-adjusted models, baseline and hyperemic shear stress were related to brachial artery percent dilation. In stepwise multivariable analyses examining clinical correlates of percent dilation (without shear stress in the model), age, sex, mean arterial pressure, pulse pressure, heart rate, body mass index, lipid medication use, and hormone replacement therapy were related to percent dilation (R2=0.189; P<0.001). When hyperemic shear stress was incorporated, the overall R2 improved (R2=0.335; P<0.001), but relationships between risk factors and percent dilation were attenuated (age and mean arterial pressure) or no longer significant (all others). In contrast, risk factors were related to baseline and hyperemic shear stress in multivariable analyses. Evoked hyperemic shear stress is a major correlate of brachial artery flow-mediated dilation. The associations between many risk factors and brachial artery flow-mediated dilation may be attributable to reduced stimulus for dilation rather than impaired local conduit artery response during hyperemia.

Adult↗

PubMed2004

Framingham risk score and prediction of lifetime risk for coronary heart disease.

We investigated whether the Framingham risk score, which was designed to estimate the 10-year risk of coronary heart disease (CHD), differentiates lifetime risk for CHD. All subjects in the Framingham Heart Study examined from 1971 to 1996 who were free of CHD were included. Subjects were stratified into age- and gender-specific tertiles of Framingham risk score, and lifetime risk for CHD was estimated. We followed 2,716 men and 3,500 women; 939 developed CHD and 1,363 died free of CHD. At age 40 years, in risk score tertiles 1, 2, and 3, respectively, the lifetime risks for CHD were 38.4%, 41.7%, and 50.7% for men and 12.2%, 25.4%, and 33.2% for women. At age 80 years, risks were 16.4%, 17.4%, and 38.8% for men and 12.8%, 22.4%, and 27.4% for women. The Framingham risk score stratified lifetime risk well for women at all ages. It performed less well in younger men but improved at older ages as remaining life expectancy approached 10 years. Lifetime risks contrasted sharply with shorter term risks: at age 40 years, the 10-year risks of CHD in tertiles 1, 2, and 3, respectively, were 0%, 2.2%, and 11.6% for men and 0%, 0.7%, and 2.3% for women. The Framingham 10-year CHD risk prediction model discriminated short-term risk well for men and women. However, it may not identify subjects with low short-term but high lifetime risk for CHD, likely due to changes in risk factor status over time. Further work is needed to generate multivariate risk models that can reliably predict lifetime risk for CHD.

Adult↗

PubMed2004

Serum aldosterone and the incidence of hypertension in nonhypertensive persons.

BACKGROUND: Primary hyperaldosteronism is a well-recognized cause of secondary hypertension. It is unknown whether serum aldosterone levels within the physiologic range influence the risk of hypertension. METHODS: We investigated the relation of baseline serum aldosterone levels to increases in blood pressure and the incidence of hypertension after four years in 1688 nonhypertensive participants in the Framingham Offspring Study (mean age, 55 years), 58 percent of whom were women. We defined an increase in blood pressure as an increment of at least one blood-pressure category (as defined by the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure) and defined hypertension as a systolic blood pressure of 140 mm Hg or higher, a diastolic blood pressure of 90 mm Hg or higher, or the use of antihypertensive medications. RESULTS: At follow-up, the blood-pressure category had increased in 33.6 percent of the participants, and hypertension had developed in 14.8 percent. In multivariable models, a 16 percent increase in the risk of an elevation in blood pressure (P=0.002) and a 17 percent increase in the risk of hypertension (P=0.03) were observed per quartile increment in the serum aldosterone level. The highest serum aldosterone quartile, relative to the lowest, was associated with a 1.60-fold risk of an elevation in blood pressure (95 percent confidence interval, 1.19 to 2.14) and a 1.61-fold risk of hypertension (95 percent confidence interval, 1.05 to 2.46). The associations between the serum aldosterone level and blood-pressure outcomes were not significantly affected by adjustment for urinary sodium excretion or left ventricular thickness or internal dimensions. CONCLUSIONS: In our community-based sample, increased aldosterone levels within the physiologic range predisposed persons to the development of hypertension.

Aldosterone↗

PubMed2004

Genome-wide scan for pulse pressure in the National Heart, Lung and Blood Institute's Framingham Heart Study.

The objective of this study was to assess heritability and identify chromosomal regions showing evidence of linkage to pulse pressure (PP), a simple indicator of proximal conduit vessel stiffness. Blood pressure data were analyzed for 8478 members of the National Heart, Lung and Blood Institute's (NHLBI) Framingham Heart Study. Long-term PP was defined using 2-stage analysis. First, the difference between systolic and diastolic blood pressure was averaged over all qualifying clinic examinations. In the second stage, mean PP was adjusted for mean age, time period of examination, and body mass index by regression analysis. PP values were available for 6421 individuals in 1593 families for heritability estimation and for 2492 individuals in 330 families for linkage analysis. Microsatellite markers covering the genome at 10 cM intervals were typed by the NHLBI Mammalian Genotyping Service; genome scan data were available on 1585 individuals with PP data. Heritability estimates of long-term PP accounting for hypertension treatment and for ignoring treatment were 0.52 and 0.51, respectively. Variance component linkage analysis identified several locations with suggestive evidence of linkage: chromosome 15 at 122 cM (logarithm of odds [LOD]=2.94), chromosome 7 at 71 cM (LOD=2.42), chromosome 5 at 53 cM (LOD=2.03), and chromosome 10 at 81 cM (LOD=1.83) for PP accounting for treatment. LOD scores were slightly lower when ignoring treatment, with the exception of a peak on chromosome 10 at 81 cM (LOD=2.58). In conclusion, we have demonstrated a substantial genetic component to PP and have identified 4 chromosomal regions that may harbor genes influencing vascular stiffness.

Blood Pressure↗

PubMed2004

Parental atrial fibrillation as a risk factor for atrial fibrillation in offspring.

CONTEXT: Atrial fibrillation (AF) is the most common cardiac dysrhythmia in the United States. Whereas rare cases of familial AF have been reported, it is unknown if AF among unselected individuals is a heritable condition. OBJECTIVE: To determine whether parental AF increases the risk for the development of offspring AF. DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study (1983-2002) within the Framingham Heart Study, a population-based epidemiologic study. Participants were 2243 offspring (1165 women, 1078 men) at least 30 years of age and free of AF whose parents had both been evaluated in the original cohort. MAIN OUTCOME MEASURES: Development of new-onset AF in the offspring was prospectively examined in association with previously documented parental AF. RESULTS: Among 2243 offspring participants, 681 (30%) had at least 1 parent with documented AF; 70 offspring participants (23 women; mean age, 62 [range, 40-81] years) developed AF in follow-up. Compared with no parental AF, AF in at least 1 parent increased the risk of offspring AF (multivariable-adjusted odds ratio [OR], 1.85; 95% confidence interval [CI], 1.12-3.06; P =.02). These results were stronger when age was limited to younger than 75 years in both parents and offspring (multivariable-adjusted OR, 3.23; 95% CI, 1.87-5.58; P<.001) and when the sample was further limited to those without antecedent myocardial infarction, heart failure, or valve disease (multivariable-adjusted OR, 3.17; 95% CI, 1.71-5.86; P<.001). CONCLUSIONS: Parental AF increases the future risk for offspring AF, an observation supporting a genetic susceptibility to developing this dysrhythmia. Further research into the genetic factors predisposing to AF is warranted.

Adult↗

PubMed2004

Relations of plasma matrix metalloproteinase-9 to clinical cardiovascular risk factors and echocardiographic left ventricular measures: the Framingham Heart Study.

BACKGROUND: Plasma levels of matrix metalloproteinase-9 (MMP-9), a key determinant of extracellular matrix degradation, are increased in heart failure and in acute coronary syndromes. We investigated cross-sectional relations of plasma MMP-9 to vascular risk factors and echocardiographic left ventricular (LV) measurements. METHODS AND RESULTS: We studied 699 Framingham Study participants (mean age, 57 years; 58% women), free of heart failure and previous myocardial infarction, who underwent routine echocardiography. We examined sex-specific distributions of LV internal dimensions (LVEDD) and wall thickness (LVWT) and sampled persons with both LVEDD and LVWT below the sex-specific median (referent, n=299), with increased LVEDD (LVEDD > or =90th percentile, n=204) and increased LVWT (LVWT > or =90th percentile, n=221) in a 3:2:2 ratio. Plasma MMP-9 was detectable in 138 persons (20%). In multivariable models, increasing heart rate (OR per SD, 1.41; 95% CI, 1.17 to 1.71) and antihypertensive treatment (OR, 1.63; 95% CI, 1.06 to 2.50) were key clinical correlates of detectable plasma MMP-9. In multivariable-adjusted models, detectable plasma MMP-9 was associated with increased LVEDD (OR, 2.84; 95% CI, 1.13 to 7.11), increased LVWT (OR, 2.54; 95% CI, 1.00 to 6.46), and higher LV mass (P=0.06) in men but not in women (OR for increased LVEDD, 1.37; 95% CI, 0.54 to 3.46; for increased LVWT, 0.99; 95% CI, 0.39 to 2.52; P=0.59 for LV mass). CONCLUSIONS: In our community-based sample, detectable plasma MMP-9 levels were associated with increased LV diastolic dimensions and increased wall thickness in men. These observations indicate that plasma MMP-9 level may be a marker for cardiac extracellular matrix degradation, a process involved in LV remodeling.

Aged↗

PubMed2004

CCAAT/enhancer-binding protein alpha (C/EBPalpha) activates transcription of the human microsomal epoxide hydrolase gene (EPHX1) through the interaction with DNA-bound NF-Y.

Microsomal epoxide hydrolase (mEH) plays a central role in xenobiotic metabolism as well as mediating the sodium-dependent uptake of bile acids into the liver, where these compounds regulate numerous biological processes such as cholesterol metabolism and hepatocyte signaling pathways. Little is known, however, about the factors that control the constitutive and inducible expression of the mEH gene (EPHX1) that is altered during development and in response to numerous xenobiotics. In previous studies we have established that GATA-4 binding to the EPHX1 core promoter is critical for EPHX1 expression. The -80/+25 bp core promoter also contained a reversed CCAAT box (-5/-1 bp), integrity of which was required for maximal basal EPHX1 transcription in HepG2 cells. Transient transfection of CCAAT/enhancer-binding protein alpha (C/EBPalpha) substantially stimulated EPHX1 promoter activity. Electrophoretic mobility shift assays, however, revealed that nuclear factor Y (NF-Y), but not C/EBPalpha, directly bound to this site although increased expression of NF-Y had no effect on EPHX1 promoter activity. These results suggested that C/EBPalpha activated EPHX1 expression through its interaction with NF-Y bound to the CCAAT box. The existence of a C/EBPalpha[NF-Y] complex was supported by electrophoretic mobility shift assays using antibodies against NF-Y and C/EBPalpha as well as by the ability of a dominant-negative NF-Y expression vector to inhibit promoter activity. The interaction between these transcription factors was established by co-immunoprecipitation analysis and glutathione S-transferase pull-down assays, whereas the association of the two factors and the interaction of NF-Y with the CCAAT box in vivo was confirmed by chromatin immunoprecipitation assays. C/EBPalpha-dependent EPHX1 activation was also supported by reconstitution studies in HeLa cells that lack this protein. These results establish that EPHX1 expression is regulated by C/EBPalpha interacting with DNA-bound NF-Y.

CCAAT-Binding Factor↗

PubMed2004

Clinical correlates and prognostic significance of exercise-induced ventricular premature beats in the community: the Framingham Heart Study.

BACKGROUND: Recent investigations suggest that ventricular premature beats during exercise (EVPBs) are associated with increased cardiovascular mortality in asymptomatic individuals, but mechanisms underlying the association are unclear. METHOD AND RESULTS: We evaluated 2885 Framingham Offspring Study participants (1397 men; mean age, 43 years) who were free of cardiovascular disease and who underwent a routine exercise stress test; 792 participants (27%) had development of EVPBs (median, 0.22/min of exercise). Logistic regression was used to evaluate predictors of EVPBs. Cox models were used to examine the relations of infrequent (less than or equal to median) and frequent (greater than median) versus no EVPBs to incidence of hard coronary heart disease (CHD) event (recognized myocardial infarction, coronary insufficiency, or CHD death) and all-cause mortality, adjusting for vascular risk factors and exercise variables. Age and male sex were key correlates of EVPBs. During follow-up (mean, 15 years), 142 (113 men) had a first hard CHD event and 171 participants (109 men) died. EVPBs were not associated with hard CHD events but were associated with increased all-cause mortality rates (multivariable-adjusted hazards ratio, 1.86, 95% CI, 1.24 to 2.79 for infrequent, and 1.71, 95% CI, 1.18 to 2.49 for frequent EVPBs versus none). The relations of EVPBs to mortality risk were not influenced by VPB grade, presence of recovery VPBs, left ventricular dysfunction, or an ischemic ST-segment response. CONCLUSIONS: In our large, community-based sample of asymptomatic individuals, EVPBs were associated with increased risk of death at a much lower threshold than previously reported. Additional studies are needed to confirm these findings and to clarify the underlying mechanisms.

Adult↗

PubMed2004

Parental cardiovascular disease as a risk factor for cardiovascular disease in middle-aged adults: a prospective study of parents and offspring.

CONTEXT: Whether parental cardiovascular disease confers increased risk independent of other risk factors remains controversial. Prior studies relied on offspring report, without complete validation of parental events. OBJECTIVE: To determine whether parental cardiovascular disease predicts offspring events independent of traditional risk factors, using a prospective design for both parents and offspring, and uniform criteria to validate events. DESIGN: Inception cohort study. SETTING: Framingham Heart Study, a US population-based epidemiologic cohort begun in 1948 with the offspring cohort established in 1971. PARTICIPANTS: All Framingham Offspring Study participants (aged > or =30 years) who were free of cardiovascular disease and both parents in the original Framingham cohort. MAIN OUTCOME MEASURES: We examined the association of parental cardiovascular disease with 8-year risk of offspring cardiovascular disease, using pooled logistic regression. RESULTS: Among 2302 men and women (mean age, 44 years), 164 men and 79 women had cardiovascular events during follow-up. Compared with participants with no parental cardiovascular disease, those with at least 1 parent with premature cardiovascular disease (onset age <55 years in father, <65 years in mother) had greater risk for events, with age-adjusted odds ratios of 2.6 (95% confidence interval [CI], 1.7-4.1) for men and 2.3 (95% CI, 1.3-4.3) for women. Multivariable adjustment resulted in odds ratios of 2.0 (95% CI, 1.2-3.1) for men and 1.7 (95% CI, 0.9-3.1) for women. Nonpremature parental cardiovascular disease and parental coronary disease were weaker predictors. Addition of parental information aided in discriminating event rates, notably among offspring with intermediate levels of cholesterol and blood pressure, as well as intermediate predicted multivariable risk. CONCLUSIONS: Using validated events, we found that parental cardiovascular disease independently predicted future offspring events in middle-aged adults. Addition of parental information may help clinicians and patients with primary prevention of cardiovascular disease, when treatment decisions may be difficult in patients at intermediate risk based on levels of single or multiple risk factors. These data also support further research into genetic determinants of cardiovascular risk.

Adult Children↗

PubMed2004

Changes in arterial stiffness and wave reflection with advancing age in healthy men and women: the Framingham Heart Study.

With advancing age, arterial stiffness and wave reflections increase and elevate systolic and pulse pressures. An elevated central pulse pressure is generally ascribed to increased wave reflection and portends an unfavorable prognosis. Using arterial tonometry, we evaluated central (carotid-femoral) and peripheral (carotid-brachial) pulse wave velocity, amplitudes of forward and reflected pressure waves, and augmentation index in 188 men and 333 women in the Framingham Heart Study offspring cohort who were free of clinical cardiovascular disease, hypertension, diabetes, smoking within the past 12 months, dyslipidemia, and obesity. In multivariable linear regression models, advancing age was the predominant correlate of higher carotid-femoral pulse wave velocity; other correlates were higher mean arterial pressure, heart rate, and triglycerides and walk test before tonometry (model R2=0.512, P<0.001). A similar model was obtained for carotid-brachial pulse wave velocity (model R2=0.227, P<0.001), although the increase with advancing age was smaller. Owing to different relations of age to central and peripheral stiffness measures, carotid-femoral pulse wave velocity was lower than carotid-brachial pulse wave velocity before age 50 years but exceeded it thereafter, leading to reversal of the normal central-to-peripheral arterial stiffness gradient. In this healthy cohort with a minimal burden of cardiovascular disease risk factors, an age-related increase in aortic stiffness, as compared with peripheral arterial stiffness, was associated with increasing forward wave amplitude and pulse pressure and reversal of the arterial stiffness gradient. This phenomenon may facilitate forward transmission of potentially deleterious pressure pulsations into the periphery.

Adult↗

PubMed2004

Long-term alcohol consumption and the risk of atrial fibrillation in the Framingham Study.

Atrial fibrillation (AF) is a major risk factor for stroke. Although acute alcohol intake has been associated with AF, it is not known whether long-term alcohol consumption in moderation is associated with an increased risk of AF. We used a risk set method to assess the relation of long-term alcohol consumption to the risk of AF among participants in the Framingham Study. For each case, up to 5 controls were selected and matched for age, age at baseline examination, sex, cohort, baseline history of hypertension, congestive heart failure, and myocardial infarction. Within each risk set, alcohol consumption was averaged from baseline until the examination preceding the index case of AF. Of the 1,055 cases of AF occurring during a follow-up of >50 years, 544 were men and 511 were women. In a conditional logistic regression with additional adjustment for systolic blood pressure, age at baseline examination, education, and cumulative history of myocardial infarction, congestive heart failure, diabetes mellitus, left ventricular hypertrophy, and valvular heart disease, the relative risks were 1.0 (reference), 0.97 (95% confidence interval [CI] 0.78 to 1.22), 1.06 (95% CI 0.80 to 1.38), 1.12 (95% CI 0.80 to 1.55), and 1.34 (95% CI 1.01 to 1.78) for alcohol categories of 0, 0.1 to 12, 12.1 to 24, 24.1 to 36, and >36 g/day, respectively. In conclusion, our data indicate little association between long-term moderate alcohol consumption and the risk of AF, but a significantly increased risk of AF among subjects consuming >36 g/day (approximatively >3 drinks/day).

Adult↗

PubMed2004

Metacarpal cortical area and risk of coronary heart disease: the Framingham Study.

The objective of this study was to determine the relation between bone mass and the incidence of coronary heart disease in women and men. Participants included 2,059 cohort members of the Framingham Study (1,236 women and 823 men aged 47-80 years) who underwent posteroanterior hand radiography and were free from cardiovascular disease at baseline (1967-1970) and who were then followed for 30 years through the end of 1997 for the incidence of coronary heart disease. The incidence of coronary heart disease decreased from 15.65/1,000 person-years among women in the lowest metacarpal cortical area quartile to 11.76/1,000 person-years among women in the highest quartile (p(trend) = 0.03), and the inverse relation persisted after adjustment for confounders (highest vs. lowest quartile of metacarpal cortical area: hazard ratio = 0.73, 95% confidence interval: 0.53, 1.00; p(trend) = 0.03). In contrast, no association was present in men (highest vs. lowest quartile of metacarpal cortical area: hazard ratio = 1.14, 95% confidence interval: 0.84, 1.56; p(trend) = 0.55).

Aged↗