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Biomedical subjects

Daniel Levy

Publications and source records attributed to Daniel Levy.

At least 127 records · Page 7Linked to original sources
PubMed2003

Doppler transmitral flow indexes and risk of atrial fibrillation (the Framingham Heart Study).

Atrial fibrillation (AF) is characterized by structural remodeling and atrial systolic failure. It is unclear if atrial filling abnormalities precede the onset of AF. We evaluated 942 Framingham Study subjects (587 women; mean age 75 years) who underwent Doppler echocardiographic evaluation at a routine examination and who did not have a history of AF. We used multivariable Cox regression models (stratified by gender and prevalent cardiovascular disease) to examine the relations of Doppler transmitral flow indexes (ratio of the velocity-time integrals of the early [E] and late [A] diastolic filling waves [VTI E/A], a correlate of atrial conduit function; E-wave deceleration time; the atrial filling fraction, an index of atrial systolic function; and peak A wave velocity) to the incidence of AF. At follow-up (mean 7 years), 85 subjects (41 women) developed AF. In models adjusting for established risk factors for AF (including left atrial size) at baseline, and for heart failure and myocardial infarction on follow-up, a 1 SD increment in VTI E/A was associated with a 28% increase in risk of AF (hazards ratio 1.28, 95% confidence interval 1.02 to 1.59). A 1 SD decrease in the atrial filling fraction was associated with a 28% higher risk of AF (hazards ratio 1.28, 95% confidence interval 0.98 to 1.67). There was a U-shaped relation between peak A-wave velocity and risk of AF. Thus, in our elderly community-based sample, increased VTI E/A and a low atrial filling fraction were markers of increased risk of AF, suggesting that altered atrial filling may antedate AF.

Aged↗
PubMed2003

Development and validation of a stability-indicating high performance liquid chromatographic assay for benoxinate.

Benoxinate is a local anaesthetic used for ophthalmic applications. The aim of this study was to develop a rapid and simple stability-indicating method for the determination of benoxinate formulated for ophthalmic use, evaluate its long-term stability and identify its major degradation product. Benoxinate was eluted on a 10 microm Spherisorb phenyl column, 250 x 3.2 mm, with a mobile phase consisting of acetonitrile-buffer (pH 3.5) (35:65, v/v), pumped at 0.8 ml min(-1) flow rate. The buffer was composed of sodium dihydrogen phosphate (50 mM), sodium hydrogen sulfate (2.5 mM) and 1-heptanesulfonic acid sodium salt (5 mM). The analyte was quantified spectrophotometrically at 308 nm. The chromatograms of benoxinate formulations obtained by this method showed benoxinate (t = 4.5 min) well resolved from its degradation product (t = 2.3 min), which was separately identified by means of HPLC-MS as 4-amino-3-butoxybenzoic acid. The assay was demonstrated to have high accuracy, precision and linearity. The method was implemented in investigating the long-term stability of benoxinate 0.4% ophthalmic solutions. The method was found to be simple, quick and selective in determining benoxinate concentrations in fresh and aged preparations.

Anesthetics, Local↗
PubMed2003

A genome-wide search for genes affecting circulating fibrinogen levels in the Framingham Heart Study.

INTRODUCTION: Circulating levels of fibrinogen are associated with atherosclerosis and predict future coronary heart disease and stroke. Levels of fibrinogen are correlated among family members, suggesting a heritable component. Variants of the beta-fibrinogen gene subunit on 4q28 are associated with fibrinogen levels but explain only a small proportion of the total genetic variability. It remains unknown what role, if any, is played by other genetic variants in the inter-individual variability in levels of fibrinogen in the general population. MATERIALS AND METHODS: We conducted a 10-cM spaced genome-wide scan using 402 original cohort subjects and 1193 offspring subjects from 330 extended families of the Framingham Heart Study. Heritability and linkage analyses were carried out using variance component methods. Regression analyses were performed to adjust for traditional risk factors and HindIII beta-148 genotypes. RESULTS AND DISCUSSIONS: The total heritability was estimated as 0.24. The highest and second highest LOD scores of linkage were found on chromosomes 2 (LOD=1.5 at 243 cM) and 10 (LOD=2.4 at 87 cM) using only offspring subjects in the analysis, and on chromosomes 2 (LOD=2.1 at 242 cM) and 10(LOD=1.4 at 86 cM), 17 (LOD=1.4 at 96 cM) and 20 (LOD=1.4 at 80 cM) using both original cohort and offspring. These results suggest that there may be influential genetic regions on these chromosomes. While no linkage with genome-wide significance was detected, further research to confirm our findings is warranted.

Adult↗
PubMed2003

Inflammatory markers and risk of heart failure in elderly subjects without prior myocardial infarction: the Framingham Heart Study.

BACKGROUND: Experimental studies support a key role for cytokines in left ventricular remodeling. In congestive heart failure (CHF) patients, elevated plasma cytokine levels are associated with worse functional status and adverse prognosis. It is unclear whether cytokine levels can predict the incidence of CHF in asymptomatic individuals. METHODS AND RESULTS: We investigated the relations of serum interleukin-6 (IL-6), C-reactive protein (CRP), and spontaneous production of tumor necrosis factor-alpha (TNFalpha) by peripheral blood mononuclear cell (PBMC) to CHF incidence among 732 elderly Framingham Study subjects (mean age 78 years, 67% women) free of prior myocardial infarction and CHF. On follow-up (mean 5.2 years), 56 subjects (35 women) developed CHF. After adjustment for established risk factors, including the occurrence of myocardial infarction on follow-up, there was a 60 (PBMC TNFalpha) to 68% (serum IL-6) increase in risk of CHF per tertile increment in cytokine concentration (P=0.04, and 0.03, respectively, for trend). A serum CRP level > or =5 mg/dL was associated with a 2.8-fold increased risk of CHF (P=0.02). Subjects with elevated levels of all 3 biomarkers (serum IL-6 and PBMC TNFalpha >median values, CRP> or =5 mg/dL) had a markedly increased risk of CHF (hazards ratio 4.07 [95% CI 1.34 to 12.37], P=0.01) compared with the other subjects. CONCLUSIONS: In our elderly, community-based sample, a single determination of serum inflammatory markers, particularly elevated IL-6, was associated with increased risk of CHF in people without prior myocardial infarction. Additional epidemiological investigations are warranted to confirm the contribution of inflammation to the pathogenesis of CHF in the general population.

Aged↗
PubMed2003

Mitral annular calcification predicts cardiovascular morbidity and mortality: the Framingham Heart Study.

BACKGROUND: Mitral annular calcification (MAC) has been associated with stroke in longitudinal, community-based cohorts and cardiovascular disease (CVD) outcomes in many small retrospective studies. Prospective data are limited on the relation of MAC with CVD morbidity and mortality. METHODS AND RESULTS: We examined the association between MAC assessed by M-mode echocardiography and the incidence of CVD, CVD death, and all-cause death over 16 years of follow-up in the Framingham Heart Study subjects who attended a routine examination between 1979 and 1981. Cox proportional hazards models were used to estimate hazard ratios (HRs) associated with the presence of MAC for each outcome. Of 1197(445 male, 752 female) subjects who had adequate echocardiographic assessment, 14% had MAC. There were 307 incident CVD events and 621 deaths. In multivariable adjusted analyses, MAC was associated with an increased risk of incident CVD (HR, 1.5; 95% CI, 1.1, 2.0), CVD death (HR, 1.6; 95% CI, 1.1, 2.3), and all-cause death (HR, 1.3; 95% CI, 1.04, 1.6). For each 1-mm increase in MAC, the risk of incident CVD, CVD death, and all-cause death increased by approximately 10%. CONCLUSIONS: The independent association of MAC with incident CVD and CVD death underscores that cardiac calcification is a marker of increased CVD risk.

Adult↗
PubMed2003

Plasma homocysteine and risk for congestive heart failure in adults without prior myocardial infarction.

CONTEXT: Elevated plasma homocysteine levels are associated with increased risk of vascular disease. It is unclear whether elevated homocysteine levels are a risk factor for congestive heart failure (CHF). OBJECTIVE: To study prospectively the association between nonfasting plasma homocysteine and incidence of CHF. DESIGN, SETTING, AND PARTICIPANTS: Community-based prospective cohort study of 2491 adults (mean age 72 years, 1547 women) who participated in the Framingham Heart Study during the 1979-1982 and 1986-1990 examinations and were free of CHF or prior myocardial infarction (recognized or unrecognized) at baseline. MAIN OUTCOME MEASURE: Incidence of a first episode of CHF during an 8-year follow-up period. RESULTS: During follow-up, 156 subjects (88 women) developed CHF. In multivariable analyses controlling for established risk factors for CHF including the occurrence of myocardial infarction (recognized or unrecognized) during follow-up, plasma homocysteine levels higher than the sex-specific median value were associated with an adjusted hazards ratio for heart failure of 1.93 in women (95% confidence interval, 1.19-3.14) and 1.84 in men (95% confidence interval, 1.06-3.17). The relation of plasma homocysteine levels to CHF risk was more continuous in women than in men. In analyses restricted to participants without any manifestation of coronary heart disease at baseline, the association of plasma homocysteine levels with risk of CHF was maintained in men and women. CONCLUSIONS: An increased plasma homocysteine level independently predicts risk of the development of CHF in adults without prior myocardial infarction. Additional investigations are warranted to confirm these findings.

Aged↗
PubMed2003

Plasma brain natriuretic peptide levels and blood pressure tracking in the Framingham Heart Study.

Increased brain natriuretic peptide (BNP) expression in the ventricles antedates elevated blood pressure (BP) in experimental studies. We hypothesized that higher plasma BNP levels in nonhypertensive individuals may be associated with a greater likelihood of future BP increase and/or hypertension. We evaluated the relations of plasma BNP to longitudinal BP tracking and incidence of hypertension in 1801 nonhypertensive Framingham Heart Study participants (mean age, 56 years; 57% women) by using gender-specific multivariable logistic regression. Progression of BP stage was defined as an increment of one or more BP categories, as classified by the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI). Hypertension was defined as a systolic BP > or =140 or diastolic BP > or =90 mm Hg or use of antihypertensive medications. On follow-up 4 years from baseline, progression of BP category was observed in 36.2% of men and 33.1% of women; hypertension developed in 16.4% of men and 15.5% of women. In multivariable models adjusting for known risk factors, elevated plasma BNP level was associated with increased risk of BP progression in men (odds ratio of 1.15 for trend across categories, P=0.046) but not in women (P=0.82). There were no significant trends of increasing incidence of hypertension across BNP categories in men or women. In our community-based sample, higher plasma BNP levels were associated with increased risk of BP progression in men but not women. Additional investigations are warranted to confirm these findings and elucidate the basis for these gender-related differences.

Blood Pressure↗
PubMed2003

Impact of glucose intolerance and insulin resistance on cardiac structure and function: sex-related differences in the Framingham Heart Study.

BACKGROUND: Although insulin resistance has been implicated in the pathogenesis of left ventricular (LV) hypertrophy, previous studies have yielded inconsistent results and are limited by referral bias. METHODS AND RESULTS: We examined the relations between echocardiographic LV measurements and glucose tolerance status in 2623 Framingham Study subjects (1514 women, mean age 53 years) free of myocardial infarction and heart failure. We also evaluated the relations of insulin resistance (homeostasis model, HOMA-IR) and LV and left atrial (LA) measures within the normal and abnormal glucose tolerance categories (the latter included impaired glucose tolerance, impaired fasting glucose, and newly diagnosed diabetes). LV mass (adjusted for age, height, heart rate, and systolic blood pressure) increased across categories of worsening glucose tolerance; the trend was more striking in women (P<0.001) compared with men (P=0.054). In subjects with normal (n=2022) and abnormal glucose tolerance (n=327), covariate-adjusted LV mass and LV wall thickness increased across HOMA-IR quartiles in women (P<0.001) but not men. In contrast, covariate-adjusted LA size increased with worsening glucose tolerance and across HOMA-IR quartiles in the normal and abnormal glucose tolerance groups in both sexes. Adjustment for body mass index considerably attenuated the relations of LV/LA measures and HOMA-IR, rendering them statistically nonsignificant in the normal glucose tolerance group. CONCLUSIONS: In our large community-based sample, LV mass and wall thickness increased with worsening glucose intolerance, an effect that was more striking in women compared with men. Insulin resistance was associated with increased LV mass in women alone, but this relation was largely accounted for by obesity.

Cross-Sectional Studies↗
PubMed2003

Systolic blood pressure, diastolic blood pressure, and pulse pressure as predictors of risk for congestive heart failure in the Framingham Heart Study.

BACKGROUND: Although hypertension is a principal precursor of congestive heart failure (CHF), the separate relations of systolic, diastolic, and pulse pressure with risk for heart failure have not been fully elucidated. OBJECTIVE: To examine the value of blood pressure predictors of heart failure. DESIGN: Community-based inception cohort study. SETTING: Framingham, Massachusetts. PATIENTS: 2040 free-living Framingham Heart Study participants (mean age, 61 years [range, 50 to 79 years]). MEASUREMENTS: The association of baseline systolic, diastolic, and pulse pressure with risk for incident CHF was examined in 894 men and 1146 women. Framingham Heart Study participants free of CHF at the baseline examination (performed from 1968 to 1973) were monitored for up to 24 years (mean, 17.4 years) for new-onset heart failure. Cox proportional hazards models were used to adjust for age, sex, smoking, left ventricular hypertrophy, body mass index, diabetes mellitus, high-density lipoprotein cholesterol level, and heart rate; hazard ratios and 95% CIs for blood pressure variables were estimated. RESULTS: CHF developed in 234 participants (11.8%) during the follow-up period. All three blood pressure components were related to the risk for CHF, but the relation was strongest for systolic and pulse pressure. A 1-SD (20 mm Hg) increment in systolic pressure conferred a 56% increased risk for CHF (hazard ratio, 1.56 [95% CI, 1.37 to 1.77]); similarly, a 1-SD (16 mm Hg) increment in pulse pressure conferred a 55% increased risk for CHF (hazard ratio, 1.55 [CI, 1.37 to 1.75]). These associations were unrelated to age, duration of follow-up, and initiation of treatment for hypertension during follow-up; they were also observed in patients with systolic hypertension (systolic blood pressure > or = 140 mm Hg) at the baseline examination (hazard ratio, 1.41 [CI, 1.18 to 1.69] for pulse pressure and 1.42 [CI, 1.14 to 1.76] for systolic pressure). CONCLUSIONS: Although each component of blood pressure was associated with risk for CHF, pulse and systolic pressure conferred greater risk than diastolic pressure. Increased pulse pressure may help identify hypertensive patients at high risk for overt CHF who are candidates for aggressive blood pressure control.

Aged↗
PubMed2003

Growth, telomere dynamics and successful and unsuccessful human aging.

This paper links mass trajectories with telomere dynamics to construct theoretical models of successful and unsuccessful aging in human beings. It couples parameters of telomere length in somatic cells, as expressed by the terminal restriction fragment (TRF), at birth and the rate of telomere attrition thereafter with nonlinear models of somatic growth to predict the probability of surviving disease free, based on the assumption that telomere length in replicating somatic cells is a surrogate indicator of aging determinants in humans. The models capture aspects of individual variation in successful and unsuccessful aging and the long-term consequences of rapid growth early in life.

Aging↗
PubMed2003

Age-related differences in the side effect profile of citalopram.

The authors evaluated the autonomic and cardiovascular side effects of citalopram with particular emphasis on their relation to the age of treated patients. The data that formed the basis for the U.S. Food and Drug Administration approval of citalopram were provided by Lundbeck (Copenhagen, Denmark). This database included placebo-controlled short- and long-term studies in major depressed patients. The list of side effects comprised all "heart rate and rhythm disorders" as well as "autonomic nervous system disorders" that had been reported by at least 5% more than that reported for the placebo group of subjects. The database encompassed 1344 subjects treated with citalopram (20-60 mg/day) for a period of no less than 6 weeks. Statistically significant age-related distribution was found for five side effects: bradycardia, nausea, diarrhea, sweating and headache. Bradycardia was more prevalent in elderly (>65 years) patients as compared to the younger population (2.4% vs. 0.2%, P<.05), whereas gastrointestinal side effects, sweating and headache were less prevalent in the elderly. The age-related differences in the side effect profile may be attributable to altered sensitivity of the serotonergic system.

Adolescent↗
PubMed2002

Genome scan linkage results for heart rate variability (the Framingham Heart Study).

There is a substantial heritable component to the beat-to-beat variation in heart rate. However, the molecular mechanisms underlying the control of heart rate variability (HRV) remain unknown. The present study sought to identify chromosomal regions linked to HRV phenotypes. The first 2 hours of ambulatory electrocardiographic recordings obtained from Framingham Heart Study subjects attending a routine examination were processed for HRV. HRV variables analyzed included very-low-frequency power, low-frequency power, and high-frequency power. Gender-specific residuals were used for log-transformed HRV data after adjustment for age, HR, systolic and diastolic blood pressures, and coffee and alcohol consumption. In conjunction with a 10-cM genome-wide scan, HRV data were available for 725 subjects in 230 extended families, including 390 sibling pairs. Variance component log-of-the-odds (LOD) scores were obtained. The highest multipoint LOD scores were obtained for log very-low frequency on chromosome 15 at 62 cM (LOD 1.84) and for log low frequency on chromosome 2 at 153 cM (LOD 1.81). These data suggest there may be influential genetic regions contributing to HRV. Further studies are warranted to identify genes in these regions that may influence autonomic tone. Recognition of the genetic determinants of HRV may provide additional insights into the pathophysiology of the autonomic nervous system and offer clues to its modulation.

Adult↗
PubMed2002

Lifetime risk for developing congestive heart failure: the Framingham Heart Study.

BACKGROUND: Congestive heart failure (CHF) is an increasing public health problem. METHODS AND RESULTS: Among Framingham Heart Study subjects who were free of CHF at baseline, we determined the lifetime risk for developing overt CHF at selected index ages. We followed 3757 men and 4472 women from 1971 to 1996 for 124 262 person-years; 583 subjects developed CHF and 2002 died without prior CHF. At age 40 years, the lifetime risk for CHF was 21.0% (95% CI 18.7% to 23.2%) for men and 20.3% (95% CI 18.2% to 22.5%) for women. Remaining lifetime risk did not change with advancing index age because of rapidly increasing CHF incidence rates. At age 80 years, the lifetime risk was 20.2% (95% CI 16.1% to 24.2%) for men and 19.3% (95% CI 16.5% to 22.2%) for women. Lifetime risk for CHF doubled for subjects with blood pressure >/=160/100 versus <140/90 mm Hg. In a secondary analysis, we only considered those who developed CHF without an antecedent myocardial infarction; at age 40 years, the lifetime risk for CHF was 11.4% (95% CI 9.6% to 13.2%) for men and 15.4% (95% CI 13.5% to 17.3%) for women. CONCLUSIONS: When established clinical criteria are used to define overt CHF, the lifetime risk for CHF is 1 in 5 for both men and women. For CHF occurring in the absence of myocardial infarction, the lifetime risk is 1 in 9 for men and 1 in 6 for women, which highlights the risk of CHF that is largely attributable to hypertension. These results should assist in predicting the population burden of CHF and placing greater emphasis on prevention of CHF through hypertension control and prevention of myocardial infarction.

Adult↗