Daniel Levy

..Breast and prostate cancer are two commonly diagnosed cancers in the United States. Prior work suggests that cancer causing genes and cancer susceptibility genes can be identified...

..We assessed the role of genetic variation in three subunits of the neuromuscular nicotinic acetylcholine receptor positioned on chromosome 2q, a region showing replicated evidence of linkage to blood pressure...

..Identifying genes associated with blood pressure advances our understanding of blood pressure regulation and highlights potential drug targets for the prevention or treatment of hypertension...

..Prior research yielded conflicting results about the magnitude of the association between body mass index (BMI) and chronic kidney disease (CKD)...

..Knowledge about the pathophysiological processes that determine arterial stiffness may help guide therapeutic approaches...

..Serum C-reactive protein (CRP) level is a heritable complex trait that predicts incident cardiovascular disease. We investigated the clinical and genetic sources of interindividual variability in serum CRP...

..Hence, we related a panel of biomarkers representing these pathways to plasma markers of collagen metabolism in a large community-based sample...

..Long-term blood pressure (BP) progression and its importance as a predictor of clinical outcome have not been well characterized across different periods...

..Several biological pathways are activated concomitantly during left ventricular (LV) remodeling. However, the relative contribution of circulating biomarkers representing these distinct pathways to LV geometry is unclear...

..In conclusion, serum C-reactive protein concentrations are higher in nonhypertensive offspring of parents with hypertension. These data suggest that inflammation may partly mediate the familial influences on hypertension risk...

..Parental obesity is a risk factor for offspring obesity. It is unclear whether parental obesity also confers risk for obesity-associated conditions (e.g., a proinflammatory or prothrombotic state) in the absence of offspring obesity...

..There are no data, however, on the incremental utility of a parsimonious set of biomarkers (reflecting pathways implicated in HF) for predicting HF risk in the community...

..Neither cysC nor MA was significantly associated with AAC in age- and gender- or multivariable-adjusted models. In conclusion, CKD, cysC, and MA are not associated with CAC or AAC when accounting for cardiovascular disease risk factors...

..In conclusion, circulating homocysteine, aldosterone, and BNP provide incremental information regarding risk for incident CKD and MA beyond traditional risk factors...

..1 years. CONCLUSIONS: Individuals with ALVD in the community are at high risk of CHF and death, even when only mild impairment of EF is present. Additional studies are needed to define optimal therapy for mild ALVD...

..Although impaired vascular function is hypothesized to influence the BP response during exercise, limited data exist on the association of vascular function with exercise BP in the community...

..Prior investigations have reported several single gene variants associated with CHD, stroke, HF, and AF. We report a community-based genome-wide association study of major CVD outcomes...

..We tested the hypothesis that the relative burden of CVD attributable to diabetes mellitus (DM) has increased over the past 5 decades...

..We evaluated the relative contributions of circulating biomarkers representing distinct biological pathways to the incidence of MetS and to longitudinal changes of its constituent risk factors...

..Congestive heart failure (CHF) is an increasing public health problem...

..Risk stratification may facilitate cost-effective approaches to management...

..We tested the hypothesis that pericardial fat, a unique fat deposit in close anatomic proximity to cardiac structures and autonomic fibers, is associated with prevalent AF...

..Baseline arterial measures did not associate with incident CKD or incident microalbuminuria. In summary, arterial stiffness correlates with albuminuria but not with mild-to-moderate CKD...

..Visceral (VAT) and subcutaneous adipose tissue (SAT) may confer differential metabolic risk profiles. The relations of VAT and SAT were analyzed with CKD as estimated by creatinine- and cystatin-based estimating equations...

..Excess risk was apparent at natriuretic peptide levels well below current thresholds used to diagnose heart failure...

..Recent experimental studies have highlighted the potential role of the natriuretic peptides and aldosterone in mediating salt sensitivity...

..18, 95% confidence interval 0.84 to 1.65, p = 0.34). In a community-based cohort with ≤10 years of follow-up, no significant association was observed between insulin resistance and incident AF...

..In conclusion, subjects with prolonged QRS durations, even without bundle branch block, are at increased risk for future pacemaker implantation. Such individuals may warrant monitoring for progressive conduction disease...

..In conclusion, our observations are consistent with the hypothesis that MS and insulin resistance impair vascular function predominantly through the influence of the component metabolic abnormalities that comprise MS...

..We report the results of a community-based genomewide association study of six ECG and HRV intermediate traits...

..Few investigations have evaluated the incremental usefulness of multiple biomarkers from distinct biologic pathways for predicting the risk of cardiovascular events...

..Additional studies addressing the pathogenesis, prevention, and optimal management of the joint occurrence of AF and CHF appear warranted...

..Increased arterial stiffness is a key factor in the pathogenesis of systolic hypertension and cardiovascular disease. Substantial heritability of blood-pressure (BP) and arterial-stiffness suggests important genetic contributions...

..We conducted a genome-wide association study (GWAS) in the community-based Framingham Heart Study...

..18, 95% confidence interval 0.98 to 1.43, p = 0.09). In conclusion, circulating osteoprotegerin concentration was significantly associated with incident AF in our community-based sample, possibly mediated by interim cardiovascular events...

..Our data emphasize the contribution of familial factors to the heart-failure burden in the community...

..0). CONCLUSIONS: The association between MAC and incident AF may be mediated partially through left atrial enlargement. These data suggest the importance of better understanding the mechanisms involved in cardiac valvular calcification...

..We hypothesized that this paradox is due partly to the advent of increasingly sensitive biomarkers for AMI diagnosis...

..The purpose of this study was to examine the link between LTL and the predisposition to atherosclerosis, as determined by carotid artery intimal medial thickness (IMT) in participants of the Framingham Offspring Study...

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..Left ventricular (LV) mass is a biomarker of long-standing exposure to cardiovascular disease risk factors. We hypothesized that LTL is related inversely to LV mass...

..EBCT AV calcium was associated with calcium deposits in the coronary arteries and the thoracic aorta, but these associations were confounded by age and risk factors...

..Hyperhomocysteinaemia is a risk factor for congestive heart failure, especially in women. We investigated if homocysteine promotes left ventricular (LV) remodelling...

..Data are limited with regard to the relations of low-grade albuminuria (below the microalbuminuria threshold) and incidence of cardiovascular disease (CVD) events in nondiabetic, nonhypertensive individuals...

..Additional investigations are warranted to confirm these findings...

..Echocardiographic measures of left ventricular (LV) structure and function are heritable phenotypes of cardiovascular disease...

..In conclusion, these data do not support an independent association between lipid concentrations and left ventricular structure...

..Neck circumference, a proxy for upper-body sc fat, may be a unique fat depot that confers additional cardiovascular risk above and beyond central body fat...

..Biomarkers of extracellular matrix remodeling are associated with prevalent hypertension in cross-sectional studies, but their relations to longitudinal changes in blood pressure (BP) and hypertension incidence are unknown...

..Biomarkers of multiple pathophysiological pathways have been related to incident atrial fibrillation (AF), but their predictive ability remains controversial...

..UACR may be a useful biomarker for identifying individuals most likely to develop hypertension...

..Further research is warranted to understand whether traditional and novel vascular risk factor burden, as well as metabolic derangements found in early kidney disease, can account for the CKD-MAC association...

..These data support the premise that abnormalities in multiple biological pathways antedate the onset of overt hypertension...

..16; 95% CI: 1.00 to 1.33). ARR is a heritable trait influenced by clinical and genetic factors. There is a continuous gradient of increasing risk of BP progression across ARR levels in nonhypertensive individuals...

..Little is known about the relations of natriuretic peptides and homocysteine to arterial wall stiffness in the community...

..Our findings support the concept that dynamic BP provides incremental information to BP at rest and suggest that exercise diastolic BP may be a better predictor than exercise systolic BP in this age group...

..We tested the hypothesis that leptin levels are associated with greater risk of CHF, CVD, and mortality in elderly individuals...

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..Clinical trials indicate that a sizable proportion of adults have multiple borderline coronary risk factors and may benefit from treatment...

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..35 (p <0.001). In conclusion, high CysC is associated with CVD risk factors even in the absence of CKD. The strong associations between CysC and CVD risk factors may partially explain why CysC is a strong predictor of incident CVD...

..We related plasma renin to incidence of CVD and mortality in 3408 individuals (mean age 59; 53% women) and in a hypertensive subset (n = 1413)...

..We investigated cross-sectional relations of plasma MMP-9 to vascular risk factors and echocardiographic left ventricular (LV) measurements...

..We hypothesized that subclinical cardiac and noncardiac organ dysfunction would accelerate the manifestation of HF...

..Concordance between reduced eGFR and MA and associated cardiovascular disease (CVD) and all-cause mortality according to these definitions is uncertain...

..In conclusion, in a community-based sample, correlations among subclinical atherosclerosis test results are low, and a substantial proportion has high levels of subclinical atherosclerosis detected on >or=2 imaging tests...

..Whether the associations of pericardial fat and measures of cardiac structure and function are independent of the systemic effects of obesity and visceral adiposity has not been fully explored...

..Sequence variants at the endothelial nitric oxide synthase (NOS3) locus have been associated with endothelial function measures, but replication has been limited...

..Additional studies are needed to determine whether variation in inflammatory marker genes is associated with tonometry measures...

..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...

..Factors contributing to these trends need further clarification...

..Given the high prevalence of obesity in the United States, strategies to promote optimal body weight may reduce the population burden of heart failure...

..CONCLUSIONS: Obese individuals have low circulating natriuretic peptide levels, which may contribute to their susceptibility to hypertension and hypertension-related disorders...

..CONCLUSIONS: There is a graded association between CRP and carotid atherosclerosis in women but not in men. The significance of this difference between sexes merits further investigation...

..We compared regression-based linkage to variance components linkage across time for six quantitative traits in the real data...

..Further studies are warranted to examine the prognostic implications of CRP and related cytokines for CVD in the elderly...

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..To investigate the contribution of the mitochondrial genome to hypertension and quantitative blood pressure (BP) phenotypes in the Framingham Heart Study cohort, a randomly ascertained, community-based sample...

..Our prospective study does not support the notion that a smaller AoR predisposes to hypertension...

..02) and diastolic pressure 4 years later (P=0.04). In summary, serum UA level was an independent predictor of hypertension incidence and longitudinal BP progression at short-term follow-up in our community-based sample...

..The excess risk of AF associated with obesity appears to be mediated by left atrial dilatation. These prospective data raise the possibility that interventions to promote normal weight may reduce the population burden of AF...

..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...

..The reference limits derived from this large, healthy community-based sample will aid in the identification of elevated natriuretic peptide levels in clinical practice...

..The possibility of a link between AAC and vascular compliance deserves further study...

..Increased pulse pressure may help identify hypertensive patients at high risk for overt CHF who are candidates for aggressive blood pressure control...

..Additional investigations are warranted to elucidate the mechanisms underlying the observed associations...

..Given the increasing prevalence of heart failure, additional studies are needed to develop effective strategies to detect and optimally manage individuals with asymptomatic left ventricular dysfunction in the community...

..In summary, elevated uromodulin concentrations precede the onset of CKD and associate with a common polymorphism in the UMOD region...

..Additional investigations are warranted to confirm these findings and elucidate the basis for these gender-related differences...

..Vasovagal syncope appears to have a benign prognosis...