Ramachandran S Vasan

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..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...

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..Genome-wide association studies (GWAS) provide mechanisms to investigate the genetic contributions to biomarker variability unconstrained by current knowledge of physiological relations...

..We tested for association between SNPs on the Affymetrix 100K SNP GeneChip and measures of adiposity in the Framingham Heart Study...

..Hundreds of statistical tests may be performed for a single SNP, thereby complicating interpretation of results and inhibiting identification of patterns of association...

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

..The short- and long-term risks for developing overweight or obesity are unknown...

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

..Data relating circulating CETP concentrations to CVD incidence in the community are conflicting...

..Evidence is conflicting regarding the performance of apolipoproteins vs traditional lipids for predicting coronary heart disease (CHD) risk...

..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...

..Activation of the renin-angiotensin-aldosterone system is associated with increased oxidative stress and inflammation. Therefore, LTL may be related to circulating biomarkers of the renin-angiotensin-aldosterone system...

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

..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...

..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...

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

..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...

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

..To determine the association of long-term exposure to atherosclerosis risk factors with valvular calcification...

..Few studies relating vitamin D deficiency to obesity have included direct measures of adiposity. Furthermore, the degree to which vitamin D is associated with metabolic traits after adjusting for adiposity measures is unclear...

..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...

..Aortic root remodeling in adulthood is known to be associated with cardiovascular outcomes. However, there is a lack of longitudinal data defining the clinical correlates of aortic root remodeling over the adult life course...

..Prior research has suggested that delay or avoidance of cardiovascular disease and cardiovascular disease risk factors plays an important role in longevity...

..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...

..The incremental utility of measuring both visceral and subcutaneous abdominal adipose tissue (SAT) in association with metabolic risk factors and underlying heritability has not been well described in a population-based setting...

..To evaluate the association of serum phosphorus with cardiac structure/function and incident heart failure...

..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...

..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 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...

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

..We examined the extent to which lower quantities of these circulating angiogenic cell phenotypes may be related to impaired vascular function and greater arterial stiffness...

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

..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...

..Consumption of soft drinks has been linked to obesity in children and adolescents, but it is unclear whether it increases metabolic risk in middle-aged individuals...

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

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

..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...

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

..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...

..It is unclear if circulating ADMA and L-arginine levels are related to cardiac structure and function in the general population...

..For CCA-IMT, no significant trends were observed in any of the analyses. The segment-specific association between elevated tHcy level and ICA/bulb-IMT suggests an association between tHcy and plaque formation...

..Experimental evidence identified the osteoprotegerin (OPG)/receptor activator of nuclear factor-kappaB (RANK)/RANK ligand (RANKL) pathway as a candidate system modulating vascular remodeling and cardiovascular disease (CVD)...

..Given sex-based differences in cardiac structure and remodeling, we hypothesized that variation in estrogen pathway genes might be associated with alteration of LV structure...

..In conclusion, inflammatory markers were elevated in patients with valvular calcium. Our findings suggest that much of the observed association between systemic inflammatory markers and valvular calcium may be due to shared risk factors...

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

..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...

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

..To evaluate if biomarkers reflecting left ventricular/vascular extracellular matrix remodeling are associated with cardiovascular disease (CVD) and death in the community...

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

..93 [1.15-3.24]). In our community-based sample, individuals with MetS have a high prevalence of subclinical atherosclerosis that likely contributes to the increased risk of overt CVD associated with the condition...

..This study does not support a link between SDB and endothelial dysfunction as measured by brachial artery flow-mediated dilation...

..We sought to relate circulating biomarkers of extracellular matrix turnover to site-specific measures of carotid artery atherosclerosis on duplex ultrasound...

..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...

..Higher circulating Lp-PLA(2) predicts cardiovascular disease risk, but sources of inter-individual variability are incompletely understood...

..The relation of carotid atherosclerosis to cognitive impairment and MRI indices of ischemia and aging in midlife is less clear...

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

..The precise relations among risk factors, inflammation, and nitric oxide bioavailability remain uncertain...

..It has been suggested that obesity promotes a relative natriuretic peptide deficiency, but this has been a variable finding in prior studies and the cause is unknown...

..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...

..We sought to determine the clinical factors and heritability associated with inflammation measured as circulating levels of soluble-intercellular adhesion molecule-1 (sICAM-1) in a community-based cohort...

..Multiple markers of inflammation and oxidative stress correlated with pericardial and intrathoracic fat volumes, extending the known association between regional adiposity and inflammation and oxidative stress...

..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...

..We sought to determine the prevalence, distribution, and risk factor correlates of high pericardial and intrathoracic fat deposits...

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

..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...

..They require weight control and exercise, as well as specific choices of antihypertensive agents...

..Prior studies were limited by small sample sizes and selection bias and none compared the diagnostic performance of these peptides in men and women...

..CONCLUSION: Lack of association of natriuretic peptides with OSAH indices suggests that undiagnosed OSAH may not be associated with major alterations in left ventricular function, as reflected in morning natriuretic peptide levels...

..Systemic oxidative stress causes insulin resistance in rodents. We tested the hypothesis that oxidative stress and insulin resistance are associated in humans...

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

..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...

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

..Our data suggest that blood levels may not adequately reflect the important role of heat shock proteins in prevalent CVD...

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

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

..Increased left atrial diameter (LAD) is associated with elevated risk of atrial fibrillation (AF) and cardiovascular disease. Information is limited regarding the short- or long-term correlates of LAD...

..We studied the relationship between ALT levels and these disorders in a long-term follow-up study...

..In the family-based Framingham Heart Study, we investigated heritability and candidate gene associations of systemic inflammatory biomarkers...

..We tested the association of the adipokines resistin and adiponectin with incident heart failure...

..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...

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

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

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

..We evaluated trends in the incidence of overweight and obesity over the past 50 years...

..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...

..The observation that high vitamin K status was associated with lower concentrations of inflammatory markers suggests that a possible protective role for vitamin K in inflammation merits further investigation...

..The present report presents a single multivariable risk function that predicts risk of developing all CVD and of its constituents...

..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...

..Information is limited on the longitudinal tracking of left ventricular (LV) mass over the adult life course and the determinants of such change...

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

..To examine the association between variation in estrogen-related genes and cross-sectional and longitudinal blood pressure in men and women...

..LV and vascular stiffness measures at prior examinations facilitate the evaluation of longitudinal changes and associated risk. ..

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..Our proposal will advance understanding of the role of vascular growth factors in initiating and promoting vascular stiffness, LV dysfunction and HTN. ..

..These analyses will likely identify genetic risk factors for cardiac alterations that in turn predispose individuals to heart failure. ..

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..The proposed translational research will likely yield seminal information that could directly improve our efforts to prevent CHF through the biochemical assessment of cardiac ECM remodeling. ..

..Activities for career development of the candidate are also planned in the areas of proteomics and genetic epidemiology. ..

..These analyses will likely identify genetic risk factors for cardiac alterations that in turn predispose individuals to heart failure. ..