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The management of heart failure with reduced ejection fraction (HF-REF) has improved significantly over the last two decades. In contrast, little or no progress has been made in identifying evidence-based, effective treatments for heart... more
The management of heart failure with reduced ejection fraction (HF-REF) has improved significantly over the last two decades. In contrast, little or no progress has been made in identifying evidence-based, effective treatments for heart failure with preserved ejection fraction (HF-PEF). Despite the high prevalence, mortality, and cost of HF-PEF, large phase III international clinical trials investigating interventions to improve outcomes in HF-PEF have yielded disappointing results. Therefore, treatment of HF-PEF remains largely empiric, and almost no acknowledged standards exist. There is no single explanation for the negative results of past HF-PEF trials. Potential contributors include an incomplete understanding of HF-PEF pathophysiology, the heterogeneity of the patient population, inadequate diagnostic criteria, recruitment of patients without true heart failure or at early stages of the syndrome, poor matching of therapeutic mechanisms and primary pathophysiological processes...
Research Interests: Cardiology, Clinical Trial, Exercise therapy, Medicine, Heart Failure, and 15 moreHumans, Diabetes mellitus, Diuretics, Anemia, Iron, Cardiac Arrhythmias, Homeostasis, Exercise Tolerance, Molecular Targeted Therapy, Angiotensin Converting Enzyme Inhibitors, Clinical Trials as Topic, Diastolic, Mineralocorticoid Receptor Antagonists, Cardiovascular medicine and haematology, and Angiotensin Receptor Antagonists
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Obesity is an important component of the pathophysiology of chronic diseases. Identifying epigenetic modifications associated with elevated adiposity, including DNA methylation variation, may point to genomic pathways that are... more
Obesity is an important component of the pathophysiology of chronic diseases. Identifying epigenetic modifications associated with elevated adiposity, including DNA methylation variation, may point to genomic pathways that are dysregulated in numerous conditions. The Illumina 450K Bead Chip array was used to assay DNA methylation in leukocyte DNA obtained from 2,097 African American adults in the Atherosclerosis Risk in Communities (ARIC) study. Mixed effects regression models were used to test the association of methylation beta value with concurrent BMI and waist circumference (WC), and BMI change, adjusting for batch effects and potential confounders. Replication using whole blood DNA from 2,377 White adults in the Framingham Heart Study and CD4+ T cell DNA from 991 Whites in the GOLDN Study was followed by testing using adipose tissue DNA from 648 women in the MuTHER cohort. Seventy-six (76) BMI-related probes, 164 WC-related probes, and 8 BMI change-related probes passed the th...
Research Interests: Obesity, Biology, Atherosclerosis, Medicine, Biological Sciences, and 13 moreHumans, Female, Male, Human Molecular Genetics, DNA methylation, Lipid metabolism, Body Mass Index, Waist Circumference, African Americans, Aged, Middle Aged, European Continental Ancestry Group, and Medical and Health Sciences
Research Interests: Evidence Based Medicine, Exercise therapy, Comorbidity, Humans, Hemodynamics, and 15 moreFemale, Goals, Anticoagulants, Denervation, Clinical Sciences, Aged, Circulation, Age Factors, American Heart Association, Coronary Artery Disease, Cohort Studies, Clinical Trials as Topic, Combined Modality Therapy, Antihypertensive agents, and Cardiovascular medicine and haematology
Identification of microRNA expression quantitative trait loci (miR-eQTL) can yield insights into regulatory mechanisms of microRNA transcription, and can help elucidate the role of microRNA as mediators of complex traits. Here we present... more
Identification of microRNA expression quantitative trait loci (miR-eQTL) can yield insights into regulatory mechanisms of microRNA transcription, and can help elucidate the role of microRNA as mediators of complex traits. Here we present a miR-eQTL mapping study of whole blood from 5,239 individuals, and identify 5,269 cis-miR-eQTLs for 76 mature microRNAs. Forty-nine per cent of cis-miR-eQTLs are located 300-500 kb upstream of their associated intergenic microRNAs, suggesting that distal regulatory elements may affect the interindividual variability in microRNA expression levels. We find that cis-miR-eQTLs are highly enriched for cis-mRNA-eQTLs and regulatory single nucleotide polymorphisms. Among 243 cis-miR-eQTLs that were reported to be associated with complex traits in prior genome-wide association studies, many cis-miR-eQTLs miRNAs display differential expression in relation to the corresponding trait (for example, rs7115089, miR-125b-5p and high-density lipoprotein cholestero...
Research Interests: Genetics, Computational Biology, MicroRNA, Biology, Medicine, and 14 moreMultidisciplinary, Humans, Female, Male, Gene, Aged, Middle Aged, microRNAs, Adult, Single Nucleotide Polymorphism, Quantitative Trait Loci, Nature Communications, Gene expression profiling, and reverse transcriptase polymerase chain reaction
Cardiovascular disease (CVD) reflects a highly coordinated complex of traits. Although genome-wide association studies have reported numerous single nucleotide polymorphisms (SNPs) to be associated with CVD, the role of most of these... more
Cardiovascular disease (CVD) reflects a highly coordinated complex of traits. Although genome-wide association studies have reported numerous single nucleotide polymorphisms (SNPs) to be associated with CVD, the role of most of these variants in disease processes remains unknown. We built a CVD network using 1512 SNPs associated with 21 CVD traits in genome-wide association studies (at P≤5×10(-8)) and cross-linked different traits by virtue of their shared SNP associations. We then explored whole blood gene expression in relation to these SNPs in 5257 participants in the Framingham Heart Study. At a false discovery rate <0.05, we identified 370 cis-expression quantitative trait loci (eQTLs; SNPs associated with altered expression of nearby genes) and 44 trans-eQTLs (SNPs associated with altered expression of remote genes). The eQTL network revealed 13 CVD-related modules. Searching for association of eQTL genes with CVD risk factors (lipids, blood pressure, fasting blood glucose,...
Research Interests: Gene expression, Humans, Smoking, Female, Male, and 15 moreMedical Physiology, Risk factors, Gene Regulatory Networks, Phenotype, Clinical Sciences, Adult, Single Nucleotide Polymorphism, Circulation, Quantitative Trait Loci, Cardiovascular Diseases, Genetic variation, Risk Factors, Coronary Artery Disease, Type 2 Diabetes Mellitus, and Cardiovascular medicine and haematology
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Genetic research regarding blood lipids has largely focused on DNA sequence variation; few studies have explored epigenetic effects. Genome-wide surveys of DNA methylation may uncover epigenetic factors influencing lipid metabolism. To... more
Genetic research regarding blood lipids has largely focused on DNA sequence variation; few studies have explored epigenetic effects. Genome-wide surveys of DNA methylation may uncover epigenetic factors influencing lipid metabolism. To identify whether differential methylation of cytosine-(phosphate)-guanine dinucleotides (CpGs) correlated with lipid phenotypes, we isolated DNA from CD4+ T cells and quantified the proportion of sample methylation at >450 000 CpGs by using the Illumina Infinium HumanMethylation450 Beadchip in 991 participants of the Genetics of Lipid Lowering Drugs and Diet Network. We modeled the percentage of methylation at individual CpGs as a function of fasting very-low-density lipoprotein cholesterol and triglycerides (TGs) by using mixed linear regression adjusted for age, sex, study site, cell purity, and family structure. Four CpGs (cg00574958, cg17058475, cg01082498, and cg09737197) in intron 1 of carnitine palmitoyltransferase 1A (CPT1A) were strongly a...
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Despite a growing number of reports of gene expression analysis from blood-derived RNA sources, there have been few systematic comparisons of various RNA sources in transcriptomic analysis or for biomarker discovery in the context of... more
Despite a growing number of reports of gene expression analysis from blood-derived RNA sources, there have been few systematic comparisons of various RNA sources in transcriptomic analysis or for biomarker discovery in the context of cardiovascular disease (CVD). As a pilot study of the Systems Approach to Biomarker Research (SABRe) in CVD Initiative, this investigation used Affymetrix Exon arrays to characterize gene expression of three blood-derived RNA sources: lymphoblastoid cell lines (LCL), whole blood using PAXgene tubes (PAX), and peripheral blood mononuclear cells (PBMC). Their performance was compared in relation to identifying transcript associations with sex and CVD risk factors, such as age, high-density lipoprotein, and smoking status, and the differential blood cell count. We also identified a set of exons that vary substantially between participants, but consistently in each RNA source. Such exons are thus stable phenotypes of the participant and may potentially beco...
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Research Interests: Obesity, Medicine, Insulin Resistance, Humans, Blood Pressure, and 15 moreFemale, Body Composition, Male, Regression Analysis, Body Size, Risk factors, Clinical Sciences, Aged, Middle Aged, Adult, Cardiovascular Diseases, Risk Factors, Neck, Proportional Hazards Models, and Paediatrics and reproductive medicine
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Background— Heart failure (HF) developing in hypertensive patients may occur with preserved or reduced left ventricular ejection fraction (PEF [≥50%] or REF [<50%]). In the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart... more
Background— Heart failure (HF) developing in hypertensive patients may occur with preserved or reduced left ventricular ejection fraction (PEF [≥50%] or REF [<50%]). In the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), 42 418 high-risk hypertensive patients were randomized to chlorthalidone, amlodipine, lisinopril, or doxazosin, providing an opportunity to compare these treatments with regard to occurrence of hospitalized HFPEF or HFREF. Methods and Results— HF diagnostic criteria were prespecified in the ALLHAT protocol. EF estimated by contrast ventriculography, echocardiography, or radionuclide study was available in 910 of 1367 patients (66.6%) with hospitalized events meeting ALLHAT criteria. Cox regression models adjusted for baseline characteristics were used to examine treatment differences for HF (overall and by PEF and REF). HF case fatality rates were examined. Of those with EF data, 44.4% had HFPEF and 55.6% had HFREF. Chlorthal...
Research Interests: Cardiology, Heart Failure, Humans, Hypertension, Cox Regression, and 15 moreFemale, Clinical Sciences, Aged, Circulation, Amlodipine, Ejection Fraction, Confidence Interval, Calcium Channel Blocker, Diagnostic Criteria, Antihypertensive agents, High risk, Case fatality rate, Cardiovascular medicine and haematology, Heart Failure WIth Preserved Ejection Fraction, and Doxazosin
Background— Although mortality after myocardial infarction (MI) has declined in the United States in recent decades, there have been few community-based investigations of the long-term trends in the incidence of heart failure after MI,... more
Background— Although mortality after myocardial infarction (MI) has declined in the United States in recent decades, there have been few community-based investigations of the long-term trends in the incidence of heart failure after MI, and their results appear to be conflicting. Methods and Results— We evaluated 676 Framingham Heart Study participants between 45 and 85 years of age (mean age 67 years, 34% women) who developed a first MI between 1970 and 1999. We assessed the incidence rates of heart failure and of death without heart failure in each of 3 decades (1970 to 1979, 1980 to 1989, and 1990 to 1999). We estimated the multivariable-adjusted risk of events in the latter 2 decades, with the period 1970 to 1979 serving as the referent. The 30-day incidence of heart failure after MI rose from 10% in 1970 to 1979 to 23.1% in 1990 to 1999 ( P for trend 0.003), whereas 30-day mortality after MI declined from 12.2% (1970 to 1979) to 4.1% (1990 to 1999). The 5-year incidence of heart...
Research Interests: Cardiology, Incidence Geometry, Risk, Medicine, Heart Failure, and 15 moreHumans, Internal Medicine, Female, Male, Incidence, Risk factors, Clinical Sciences, Aged, Middle Aged, Myocardial Infarction, Circulation, Risk Factors, Proportional Hazards Models, Cohort Studies, and Cardiovascular medicine and haematology
Research Interests: Risk, Medicine, Electrocardiography, Humans, United States, and 14 moreFemale, Male, Heart rate, Follow-up studies, Risk factors, Middle Aged, Adult, Sudden Cardiac Death, Risk Factors, Coronary Artery Disease, Proportional Hazards Models, QT interval, Cohort Studies, and Cardiovascular medicine and haematology
Research Interests: Cardiology, Epidemiology, Obesity, Cardiovascular disease, Medicine, and 15 moreAdipose tissue, Humans, Internal Medicine, Female, Male, Heart, Body Mass Index, Association, Aged, Middle Aged, Cardiovascular Diseases, Abdominal Fat, Pericardium, Cross Sectional Studies, and Cardiovascular medicine and haematology
Genome-wide association studies (GWAS) have identified numerous loci associated with blood pressure (BP). The molecular mechanisms underlying BP regulation, however, remain unclear. We investigated BP-associated molecular mechanisms by... more
Genome-wide association studies (GWAS) have identified numerous loci associated with blood pressure (BP). The molecular mechanisms underlying BP regulation, however, remain unclear. We investigated BP-associated molecular mechanisms by integrating BP GWAS with whole blood mRNA expression profiles in 3,679 individuals, using network approaches. BP transcriptomic signatures at the single-gene and the coexpression network module levels were identified. Four coexpression modules were identified as potentially causal based on genetic inference because expression-related SNPs for their corresponding genes demonstrated enrichment for BP GWAS signals. Genes from the four modules were further projected onto predefined molecular interaction networks, revealing key drivers. Gene subnetworks entailing molecular interactions between key drivers and BP-related genes were uncovered. As proof-of-concept, we validated SH2B3, one of the top key drivers, using Sh2b3(-/-) mice. We found that a signific...
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Hypertension-1DIAGNOSTIC UTILITY OF AND RELATIONSHIP BETWEEN SOLUBLE FMS-LIKE TYROSINE KINASE, PLACENTAL GROWTH FACTOR AND SOLUBLE ENDOGLIN LEVELS IN NORMAL AND PREECLAMPTIC PREGNANCIES 12 BEST ABSTRACTS AND TOP 20% ABSTRACTSINACTIVATION OF KS-WNK1 DOES NOT LEAD TO HYPERKALEMIC HYPERTENSION DESPI...more
METHODS: Plasma/serum samples were obtained after 30 weeks of gestation from 130 pregnant primigravid women with singleton pregnancies, 120 with PE and 100 normotensive pregnancies. PE was defined as new onset of elevated blood... more
METHODS: Plasma/serum samples were obtained after 30 weeks of gestation from 130 pregnant primigravid women with singleton pregnancies, 120 with PE and 100 normotensive pregnancies. PE was defined as new onset of elevated blood pressure> 140/90 mm Hg along with≥ 2+ proteinuria on two occasions at least 4 hours apart after 20 weeks of gestation in previously normotensive subjects. Circulating sFlt-1, sEng and PlGF levels were estimated using commercially available ELISA kits (R&D systems, USA). ...
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Although a higher heart rate is associated with an increased risk of cardiovascular disease, the mechanism is not well understood. As thrombosis has an important role in plaque development and acute coronary syndromes, the increase... more
Although a higher heart rate is associated with an increased risk of cardiovascular disease, the mechanism is not well understood. As thrombosis has an important role in plaque development and acute coronary syndromes, the increase related to heart rate may result from a prothrombotic imbalance. We investigated the relation between heart rate and thrombotic potential in 3451 participants from the Offspring Cohort of the Framingham Heart Study (mean age 54 years, 55% women). Participants were divided into quintiles based on heart rate derived from a resting electrocardiogram. Higher heart rates were associated with significant age-adjusted increases in fibrinogen, viscosity, factor VII antigen, and impaired fibrinolytic potential (plasminogen activator inhibitor and tissue plasminogen activator antigen) among men and women, and von Willebrand factor antigen among men. Fibrinogen levels were 9% higher among men with a heart rate of 80.9 ± 8.1 beats/min (quintile 5) vs. 50.0 ± 3.9 beats/min (quintile 1) (314 vs. 287 mg/dl, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001 for linear trend) and 13% higher among women (83.5 ± 7.7 beats/min vs. 53.7 ± 3.5 beats/min (330 vs. 291 mg/dl, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). The significant relations persisted after multivariate adjustment, other than among men, in whom factor VII was not significant and fibrinogen was borderline significant (p = 0.065). Higher heart rates are associated with a prothrombotic state. Because these factors are also associated with endothelial dysfunction and inflammation, these findings are consistent with an injurious effect of higher heart rates on the endothelium. Measures to reduce thrombotic potential may be of particular value in people with higher heart rates.
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Whether low diastolic blood pressure (DBP) is a risk factor for recurrent cardiovascular disease (CVD) events in persons with isolated systolic hypertension is controversial. We studied 791 individuals (mean age 75 years, 47% female, mean... more
Whether low diastolic blood pressure (DBP) is a risk factor for recurrent cardiovascular disease (CVD) events in persons with isolated systolic hypertension is controversial. We studied 791 individuals (mean age 75 years, 47% female, mean follow-up time: 8±6 years) with DBP <70 (n=225) versus 70 to 89 mm Hg (n=566) after initial CVD events in the original and offspring cohorts of the Framingham Heart Study. Recurrent CVD events occurred in 153 (68%) participants with lower DBP and 271 (48%) with higher DBP (P<0.0001). Risk of recurrent CVD events in risk factor-adjusted Cox regression was higher in those with DBP <70 mm Hg versus DBP 70 to 89 mm Hg in both treated (hazard ratio, 5.1 [95% confidence interval: 3.8-6.9] P<0.0001) and untreated individuals (hazard ratio, 11.7 [95% confidence interval: 6.5-21.1] P<0.0001; treatment interaction: P=0.71). Individually, coronary heart disease, heart failure, and stroke recurrent events were more likely with DBP…
Research Interests: Heart Failure, Stroke, Humans, Hypertension, Smoking, and 15 moreBlood Pressure, Female, Male, Recurrence, Clinical Sciences, Aged, Middle Aged, Adult, Coronary heart disease, Proportional Hazards Models, Heart Diseases, Diastole, Antihypertensive agents, systole, and Cardiovascular medicine and haematology
Research Interests: Engineering, Anthropometry, Magnetic Resonance Imaging, Aging, Biometry, and 12 moreHumans, United States, Physical sciences, Body Size, Reproducibility of Results, Population Study, Sensitivity and Specificity, Reference Values, Heart Ventricles, Cohort Studies, Sex Characteristics, and Medical and Health Sciences
An understanding of the genetic variation underlying transcript splicing is essential to dissect the molecular mechanisms of common disease. The available evidence from splicing quantitative trait locus (sQTL) studies has been limited to... more
An understanding of the genetic variation underlying transcript splicing is essential to dissect the molecular mechanisms of common disease. The available evidence from splicing quantitative trait locus (sQTL) studies has been limited to small samples. We performed genome-wide screening to identify SNPs that might control mRNA splicing in whole blood collected from 5,257 Framingham Heart Study participants. We identified 572,333 cis sQTLs involving 2,650 unique genes. Many sQTL-associated genes (40%) undergo alternative splicing. Using the National Human Genome Research Institute (NHGRI) genome-wide association study (GWAS) catalog, we determined that 528 unique sQTLs were significantly enriched for 8,845 SNPs associated with traits in previous GWAS. In particular, we found 395 (4.5%) GWAS SNPs with evidence of cis sQTLs but not gene-level cis expression quantitative trait loci (eQTLs), suggesting that sQTL analysis could provide additional insights into the functional mechanism und...
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Central pressure augmentation is associated with greater backward wave amplitude and shorter transit time and is higher in women for reasons only partially elucidated. Augmentation also is affected by left ventricular function and shapes... more
Central pressure augmentation is associated with greater backward wave amplitude and shorter transit time and is higher in women for reasons only partially elucidated. Augmentation also is affected by left ventricular function and shapes of the forward and backward waves. The goal of this study was to examine the relative contributions of forward and backward wave morphology to central pressure augmentation in men and women. From noninvasive measurements of central pressure and flow in 7437 participants (4036 women) aged from 19 to 90 years (mean age, 51 years), we calculated several variables: augmentation index, backward wave arrival time, reflection factor, forward wave amplitude, forward wave peak width, and slope of the backward wave upstroke. Linear regression models for augmentation index, adjusted for height and heart rate, demonstrated nonlinear relations with age (age: B=4.6±0.1%; P<0.001; age2: B=−4.2±0.1%; P<0.001) and higher augmentation in women (B=4.5±0.4%; P<...
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The Omapatrilat in Persons with Enhanced Risk of Atherosclerotic events (OPERA) trial is a large clinical trial of omapatrilat, a vasopeptidase inhibitor, in patients with stage 1 isolated systolic hypertension (ISH). OPERA is the first... more
The Omapatrilat in Persons with Enhanced Risk of Atherosclerotic events (OPERA) trial is a large clinical trial of omapatrilat, a vasopeptidase inhibitor, in patients with stage 1 isolated systolic hypertension (ISH). OPERA is the first study to examine whether effective antihypertensive treatment can provide survival and clinical end point benefits in older persons with this common condition. This 5-year multinational, randomized, double-blind, parallel-group, placebo-controlled, forced-titration study will be conducted in approximately 12,600 subjects randomized by approximately 1100 study centers worldwide over a recruitment period of approximately 2 years. The primary objective of OPERA is to determine whether treatment with once-daily omapatrilat (target dose 40 mg) will reduce cardiovascular (CV) morbidity and mortality in older (> or = 65 years) men and women with enhanced risk for atherosclerotic events due to stage 1 ISH plus other risk factors for which currently there ...
Research Interests: Research Design, Clinical Trial, Heart Failure, Humans, Hypertension, and 15 moreBlood Pressure, Female, Male, Placebos, Risk factors, Clinical Sciences, Middle Aged, Peripheral Vascular Disease, Protease Inhibitors, Cognitive Function, Pyridines, Risk Factors, Systolic blood pressure, Isolated Systolic Hypertension, and Diastolic Blood Pressure
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Research Interests: Engineering, Genetics, Chemistry, Cardiology, Epidemiology, and 15 moreGenetic Epidemiology, Computational Biology, Biology, Cell Biology, Cell Signaling, Gene expression, Genome Wide Association Studies, Female, Atrial Fibrillation, Gene Regulatory Networks, Aged, Cardiovascular Diseases, Gene Expression Regulation, Gene expression profiling, and Cohort Studies
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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. We investigated the relation of baseline... more
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. 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. 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. In our community-based sample, increased aldosterone levels within the physiologic range predisposed persons to the development of hypertension.
Research Interests: Epidemiology, Medicine, England, Multivariate Analysis, Humans, and 15 moreHypertension, High Blood Pressure, Blood Pressure, Aldosterone, Female, Male, Incidence, Middle Aged, Longitudinal Studies, New England, Heart Ventricles, Hyperaldosteronism, Confidence Interval, Left Ventricular, and Medical and Health Sciences
... Ann Intern Med 1961;55:33-50 Web of Science | Medline. 2. Doyle JT , Dawber TR , Kannel WB , Heslin AS , Kahn HA . ... 7. McGovern PG , Pankow JS , Shahar E , et al. Recent trends in acutecoronary heart disease -- mortality,... more
... Ann Intern Med 1961;55:33-50 Web of Science | Medline. 2. Doyle JT , Dawber TR , Kannel WB , Heslin AS , Kahn HA . ... 7. McGovern PG , Pankow JS , Shahar E , et al. Recent trends in acutecoronary heart disease -- mortality, morbidity, medical care, and risk factors. ...
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A pattern of left ventricular hypertrophy evident on the electrocardiogram is a harbinger of morbidity and mortality from cardiovascular disease. Echocardiography permits the noninvasive determination of left ventricular mass and the... more
A pattern of left ventricular hypertrophy evident on the electrocardiogram is a harbinger of morbidity and mortality from cardiovascular disease. Echocardiography permits the noninvasive determination of left ventricular mass and the examination of its role as a precursor of morbidity and mortality. We examined the relation of left ventricular mass to the incidence of cardiovascular disease, mortality from cardiovascular disease, and mortality from all causes in 3220 subjects enrolled in the Framingham Heart Study who were 40 years of age or older and free of clinically apparent cardiovascular disease, in whom left ventricular mass was determined echocardiographically. During a four-year follow-up period, there were 208 incident cardiovascular events, 37 deaths from cardiovascular disease, and 124 deaths from all causes. Left ventricular mass, determined echocardiographically, was associated with all outcome events. This relation persisted after we adjusted for age, diastolic blood pressure, pulse pressure, treatment for hypertension, cigarette smoking, diabetes, obesity, the ratio of total cholesterol to high-density lipoprotein cholesterol, and electrocardiographic evidence of left ventricular hypertrophy. In men, the risk factor-adjusted relative risk of cardiovascular disease was 1.49 for each increment of 50 g per meter in left ventricular mass corrected for the subject&#39;s height (95 percent confidence interval, 1.20 to 1.85); in women, it was 1.57 (95 percent confidence interval, 1.20 to 2.04). Left ventricular mass (corrected for height) was also associated with the incidence of death from cardiovascular disease (relative risk, 1.73 [95 percent confidence interval, 1.19 to 2.52] in men and 2.12 [95 percent confidence interval, 1.28 to 3.49] in women). Left ventricular mass (corrected for height) was associated with death from all causes (relative risk, 1.49 [95 percent confidence interval, 1.14 to 1.94] in men and 2.01 [95 percent confidence interval, 1.44 to 2.81] in women). We conclude that the estimation of left ventricular mass by echocardiography offers prognostic information beyond that provided by the evaluation of traditional cardiovascular risk factors. An increase in left ventricular mass predicts a higher incidence of clinical events, including death, attributable to cardiovascular disease.
Research Interests: Multivariate Analysis, Echocardiography, Lipids, Humans, Hypertension, and 14 moreSmoking, Blood Pressure, Female, Male, Follow-up studies, Risk factors, Middle Aged, New England, Diabetes complications, Prognosis, Risk Factors, New England Journalof Medicine, Cardiomegaly, and Medical and Health Sciences
On Sept 29, 2013, the Framingham Heart Study will celebrate 65 years since the examination of the first volunteer in 1948. During this period, the study has provided substantial insight into the epidemiology and risk factors of... more
On Sept 29, 2013, the Framingham Heart Study will celebrate 65 years since the examination of the first volunteer in 1948. During this period, the study has provided substantial insight into the epidemiology and risk factors of cardiovascular disease. The origins of the study are closely linked to the cardiovascular health of President Franklin D Roosevelt and his premature death from hypertensive heart disease and stroke in 1945. In this Review we describe the events leading to the foundation of the Framingham Heart Study, and provide a brief historical overview of selected contributions from the study.
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Research Interests: Health Behavior, Risk assessment, Comorbidity, Humans, Chronic Disease, and 15 moreFemale, Male, Risk factors, Boston, Aged, Middle Aged, Longitudinal Studies, Adult, Cardiovascular Risk Factor, Cardiovascular Diseases, Risk Factors, Risk Assessment, Cohort Studies, Disease Free Survival, and Medical and Health Sciences
Research Interests: Echocardiography, Heart Failure, Prospective studies, Humans, Congestive Heart Failure, and 15 moreFemale, Male, Massachusetts, Prevalence, Middle Aged, Adult, Survival Rate, Prognosis, Reproducibility of Results, Ejection Fraction, Case Control Study, Confidence Interval, Mortality Risk, Case Control Studies, and Cardiovascular medicine and haematology
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ABSTRACT
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This study sought to examine clinical determinants of heart rate variability and to report normative reference values for eight heart rate variability measures. Although the clinical implications of heart rate variability have been... more
This study sought to examine clinical determinants of heart rate variability and to report normative reference values for eight heart rate variability measures. Although the clinical implications of heart rate variability have been described, clinical determinants and normative values of heart rate variability measures have not been studied systematically in a large community-based population. The first 2 h of ambulatory electrocardiographic recordings obtained in Framingham Heart Study subjects attending a routine examination were reprocessed for heart rate variability. Recordings with transient or persistent nonsinus rhythm, premature beats &gt; 10% of total beats, &lt; 1-h recording time or processed time &lt; 50% of recorded time were excluded; subjects receiving antiarrhythmic medications also were excluded. Among five frequency domain and three time domain measures that were obtained, low frequency power (0.04 to 0.15 Hz), high frequency power (0.15 to 0.40 Hz) and the standard deviation of total normal RR intervals based on 2-h recordings were selected for the principal analyses. Variables with potential physiologic effects or possible technical influences on heart rate variability measures were chosen for multiple linear regression analysis. Normative values, derived from a subset of healthy subjects, were adjusted for age and heart rate. There were 2,722 eligible subjects with a mean age (+/-SD) of 55 +/- 14 years. Three separate multiple linear regression analyses revealed that higher heart rate, older age, beta-adrenergic blocking agent use, history of myocardial infarction or congestive heart failure, diuretic use, diastolic blood pressure &gt; or = 90 mm Hg, diabetes mellitus, consumption of three or more cups of coffee per day and smoking were associated with lower values of one or more heart rate variability measures, whereas longer processed time, start time in the morning, frequent supraventricular and ventricular premature beats, female gender and systolic blood pressure &gt; or = 160 mm Hg were associated with higher values. Age and heart rate were the major determinants of all three selected heart rate variability measures (partial R2 values 0.125 to 0.389). Normative reference values for all eight heart rate variability measures are presented. Age and heart rate must be taken into account when assessing heart rate variability.