John S Gottdiener

University of Maryland, College Park, CGS, Maryland, United States

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Publications (315)2739.79 Total impact

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    ABSTRACT: Background: -Increasingly, the diagnostic codes from administrative claims data are being used as clinical outcomes. Methods and results: -Data from the Cardiovascular Health Study (CHS) were used to compare event rates and risk-factor associations between adjudicated hospitalized cardiovascular events and claims-based methods of defining events. The outcomes of myocardial infarction (MI), stroke, and heart failure (HF) were defined in three ways: 1) the CHS adjudicated event (CHS[adj]); 2) selected ICD9 diagnostic codes only in the primary position for Medicare claims data from the Center for Medicare and Medicaid Services (CMS[1(st)]); and 3) the same selected diagnostic codes in any position (CMS[any]). Conventional claims-based methods of defining events had high positive predictive values (PPVs) but low sensitivities. For instance, the PPV of an ICD9 code of 410.x1 for a new acute MI in the first position was 90.6%, but this code identified only 53.8% of incident MIs. The observed event rates were low. For MI, the incidence was 14.9 events per 1000 person years for CHS[adj] MI, 8.6 for CMS[1(st)] and 12.2 for CMS[any]. In general, CVD risk factor associations were similar across the three methods of defining events. Indeed, traditional CVD risk factors were also associated with all first hospitalizations not due to an MI. Conclusions: -The use of diagnostic codes from claims data as clinical events, especially when restricted to primary diagnoses, leads to an underestimation of event rates. Additionally, claims-based events data represent a composite endpoint that includes the outcome of interest and selected (misclassified) non-event hospitalizations.
    Circulation 11/2015; DOI:10.1161/CIRCULATIONAHA.115.018610 · 14.43 Impact Factor
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    ABSTRACT: Background: There is controversy regarding whether to report concentrations of high-sensitivity cardiac troponin T (hs-cTnT) to the limit of blank (LOB) (3 ng/L) or the limit of detection (LOD) (5 ng/L) of the assay in community-based cohorts. We hypothesized that hs-cTnT concentrations between the LOB and LOD would be associated with poorer cardiovascular outcomes compared to concentrations below the LOB. Methods: hs-cTnT was analyzed in a total of 10 723 participants from the Cardiovascular Health Study (CHS), Atherosclerosis Risk in Communities (ARIC) study, and Dallas Heart Study (DHS). Participants were divided into 2 groups, those with hs-cTnT concentrations below the limit of blank (LOB) (<3 ng/L) and those with hs-cTnT between the LOB and limit of detection (LOD) (3-4.99 ng/L). Cross-sectional associations with traditional cardiovascular risk factors and cardiac structural measurements, and longitudinal associations with long-term cardiovascular outcomes of incident heart failure and cardiovascular death, were determined. Results: Participants with hs-cTnT between the LOB and LOD for all 3 cohorts were older and more likely to be male and have a higher burden of cardiovascular risk factors and structural pathology. A metaanalysis of the 3 cohorts showed participants with hs-cTnT between the LOB and LOD were at increased risk of new-onset heart failure (hazard ratio, 1.18; 95% CI, 1.02-1.38) and cardiovascular mortality (hazard ratio, 1.29; 95% CI, 1.06-1.57). Conclusions: hs-cTnT concentrations between the LOB and LOD (3-4.99 ng/L) are associated with a higher prevalence of traditional risk factors, more cardiac pathology, and worse outcomes than concentrations below the LOB (<3 ng/L).
    Clinical Chemistry 10/2015; DOI:10.1373/clinchem.2015.244160 · 7.91 Impact Factor
  • John S Gottdiener ·

    JACC. Cardiovascular imaging 09/2015; 8(9):1042-4. DOI:10.1016/j.jcmg.2015.08.002 · 7.19 Impact Factor
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    ABSTRACT: Background: -Both HIV and depression are associated with increased heart failure (HF) risk. Depression, a common comorbidity, may further increase the risk of HF among HIV+ adults. We assessed the association between HIV, depression and incident HF. Methods and results: -Veterans Aging Cohort Study (VACS) participants free from cardiovascular disease at baseline (N = 81,427; 26,908 HIV+, 54,519 HIV-) were categorized into four groups: HIV- without major depressive disorder (MDD) [reference]; HIV- with MDD; HIV+ without MDD; and HIV+ with MDD. ICD-9 codes from medical records were used to determine MDD and the primary outcome, HF. After 5.8 follow-up years, HF rates per 1000 person-years were highest among HIV+ participants with MDD (9.32; 95% CI, 8.20-10.6). In Cox proportional hazards models, HIV+ participants with MDD had significantly higher risk of HF [adjusted hazard ratio (aHR) = 1.68; 95% CI, 1.45-1.95] compared to HIV- participants without MDD. MDD was associated with HF in separate fully adjusted models for HIV- and HIV+ participants (aHR = 1.21; 1.06-1.37 and 1.29; 1.11-1.51, respectively). Among those with MDD, baseline antidepressant use was associated with lower risk of incident HF events (aHR = 0.76; 0.58-0.99). Conclusions: -Our study is the first to suggest MDD is an independent risk factor for HF in HIV+ adults. These results reinforce the importance of identifying and managing MDD among HIV+ patients. Future studies must clarify mechanisms linking HIV, MDD, antidepressants, and HF; and identify interventions to reduce HF morbidity and mortality in those with both HIV and MDD.
    Circulation 09/2015; DOI:10.1161/CIRCULATIONAHA.114.014443 · 14.43 Impact Factor
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    ABSTRACT: Mental stress can trigger myocardial ischemia, but the prevalence of mental stress-induced ischemia in CHF patients is unknown.. We characterized mental stress-induced and adenosine-induced changes in myocardial perfusion and neurohormonal activation in CHF patients with reduced LV function using single-photon emission computed tomography (SPECT) to precisely quantify segment-level myocardial perfusion. 34 coronary artery disease (CAD) patients (age 62±10 years) with CHF>3 months, ejection fraction<40% underwent both adenosine and mental stress myocardial perfusion SPECT on consecutive days. Mental stress consisted of anger recall (anger-provoking speech) followed by subtracting serial 7s). Presence and extent of myocardial ischemia was quantified using the conventional 17 segment model. 68% of patients had ≥1 ischemic segment during mental stress; 81% during adenosine. On segment-by-segment analysis, perfusion to mental stress and adenosine were highly correlated. No significant differences were found between any two time points for BNP, TNF-alpha, IL-1b, troponin, VEGF, IL-17a, MMP-9, or CRP. However, ET-1 and IL-6 increased, and IL-10 decreased, between the stressor and 30 minutes post-stress.Left ventricular end diastolic dimension was 179±65 ml at rest and increased to 217±71 after mental stress and 229±86 after adenosine (p<0.01 for both). Resting end systolic volume was 129±60 ml at rest and increased to 158±66 after mental stress (p<0.05) and 171±87 after adenosine (p0.07), with no significant differences between adenosine and mental stress. Ejection fraction was 30±12 at baseline, 29±11 with mental stress, and 28±10 with adenosine (P = NS). There was high concordance between ischemic perfusion defects induced by adenosine and mental stress, suggesting that mental stress is equivalent to pharmacologic stress in eliciting clinically significant \myocardial perfusion defects in CHF patients. Cardiac dilatation suggests clinically important changes with both conditions. Psychosocial stressors during daily life may contribute to the ischemic burden of CHF patients with CAD. Copyright © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.
    Journal of Nuclear Medicine 07/2015; 56(10). DOI:10.2967/jnumed.115.157990 · 6.16 Impact Factor
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    ABSTRACT: Fibrosis is one postulated pathway by which diabetes produces cardiac and other systemic complications. Our aim was to determine which metabolic parameters are associated with circulating fibrosis-related biomarkers transforming growth factor-β (TGF-β) and procollagen type III N-terminal propeptide (PIIINP). We used linear regression to determine the cross-sectional associations of diverse metabolic parameters, including fasting glucose, fasting insulin, body mass index, fatty acid binding protein 4, and non-esterified fatty acids, with circulating levels of TGF-β (n = 1559) and PIIINP (n = 3024) among community-living older adults in the Cardiovascular Health Study. Among the main metabolic parameters we examined, only fasting glucose was associated with TGF-β (P = 0.03). In contrast, multiple metabolic parameters were associated with PIIINP, including fasting insulin, body mass index, and non-esterified fatty acids (P<0.001, P<0.001, P=0.001, respectively). These associations remained statistically significant after mutual adjustment, except the association between BMI and PIIINP. Isolated hyperglycemia is associated with higher serum concentrations of TGF-β, while a broader phenotype of insulin resistance is associated with higher serum PIIINP. Whether simultaneous pharmacologic targeting of these two metabolic phenotypes can synergistically reduce the risk of cardiac and other manifestations of fibrosis remains to be determined. Copyright © 2015. Published by Elsevier Inc.
    Metabolism: clinical and experimental 07/2015; 64(10). DOI:10.1016/j.metabol.2015.07.013 · 3.89 Impact Factor
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    ABSTRACT: Background: Studies of patients presenting for catheter ablation suggest that premature ventricular contractions (PVCs) are a modifiable risk factor for congestive heart failure (CHF). The relationship among PVC frequency, incident CHF, and mortality in the general population remains unknown. Objectives: The goal of this study was to determine whether PVC frequency ascertained using a 24-h Holter monitor is a predictor of a decrease in the left ventricular ejection fraction (LVEF), incident CHF, and death in a population-based cohort. Methods: We studied 1,139 Cardiovascular Health Study (CHS) participants who were randomly assigned to 24-h ambulatory electrocardiography (Holter) monitoring and who had a normal LVEF and no history of CHF. PVC frequency was quantified using Holter studies, and LVEF was measured from baseline and 5-year echocardiograms. Participants were followed for incident CHF and death. Results: Those in the upper quartile versus the lowest quartile of PVC frequency had a multivariable-adjusted, 3-fold greater odds of a 5-year decrease in LVEF (odds ratio [OR]: 3.10; 95% confidence interval [CI]: 1.42 to 6.77; p = 0.005), a 48% increased risk of incident CHF (HR: 1.48; 95% CI: 1.08 to 2.04; p = 0.02), and a 31% increased risk of death (HR: 1.31; 95% CI: 1.06 to 1.63; p = 0.01) during a median follow-up of >13 years. Similar statistically significant results were observed for PVCs analyzed as a continuous variable. The specificity for the 15-year risk of CHF exceeded 90% when PVCs included at least 0.7% of ventricular beats. The population-level risk for incident CHF attributed to PVCs was 8.1% (95% CI: 1.2% to 14.9%). Conclusions: In a population-based sample, a higher frequency of PVCs was associated with a decrease in LVEF, an increase in incident CHF, and increased mortality. Because of the capacity to prevent PVCs through medical or ablation therapy, PVCs may represent a modifiable risk factor for CHF and death.
    Journal of the American College of Cardiology 07/2015; 66(2):101-9. DOI:10.1016/j.jacc.2015.04.062 · 16.50 Impact Factor
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    ABSTRACT: The purpose of this study was to determine the prevalence of clinically relevant comorbidities and measures of physical and cognitive impairment in elderly persons with incident heart failure (HF). Comorbidities and functional and cognitive impairments are common in the elderly and often associated with greater mortality risk. We examined the prevalence of 9 comorbidities and 4 measures of functional and cognitive impairments in 558 participants from the Cardiovascular Health Study who developed incident HF between 1990 and 2002. Participants were followed prospectively until mid-2008 to determine their mortality risk. Mean age of participants was 79.2 ± 6.3 years with 52% being men. Sixty percent of participants had ≥3 comorbidities, and only 2.5% had none. Twenty-two percent and 44% of participants had ≥1 activity of daily living (ADL) and ≥1 instrumental activity of daily living (IADL) impaired respectively. Seventeen percent of participants had cognitive impairment (modified mini-mental state exam score <80, scores range between 0 and 100). During follow up, 504 participants died, with 1-, 5-, and 10-year mortality rates of 19%, 56%, and 83%, respectively. In a multivariable-adjusted model, the following were significantly associated with greater total mortality risk: diabetes mellitus (hazard ratio [HR]: 1.64; 95% confidence interval [CI]: 1.33 to 2.03), chronic kidney disease (HR: 1.32; 95% CI: 1.07 to 1.62 for moderate disease; HR: 3.00; 95% CI: 1.82 to 4.95 for severe), cerebrovascular disease (HR: 1.53; 95% CI: 1.22 to 1.92), depression (HR: 1.44; 95% CI: 1.09 to 1.90), functional impairment (HR: 1.30; 95% CI: 1.04 to 1.63 for 1 IADL impaired; HR: 1.49; 95% CI: 1.07 to 2.04 for ≥2 IADL impaired), and cognitive impairment (HR: 1.33; 95% CI: 1.02 to 1.73). Other comorbidities (hypertension, coronary heart disease, peripheral arterial disease, atrial fibrillation, and obstructive airway disease) and measures of functional impairments (ADLs and 15-ft walk time) were not associated with mortality. Elderly patients with incident HF have a high burden of comorbidities and functional and cognitive impairments. Some of these conditions are associated with greater mortality risk. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
    07/2015; 3(7):542-50. DOI:10.1016/j.jchf.2015.03.004
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    ABSTRACT: Hypertension remains a major contributor to the global burden of disease. The measurement of blood pressure continues to have pitfalls related to both physiological aspects and acute variation. As the left ventricle (LV) remains one of the main target organs of hypertension, and echocardiographic measures of structure and function carry prognostic information in this setting, the development of a consensus position on the use of echocardiography in this setting is important. Recent developments in the assessment of LV hypertrophy and LV systolic and diastolic function have prompted the preparation of this document. The focus of this work is on the cardiovascular responses to hypertension rather than the diagnosis of secondary hypertension. Sections address the pathophysiology of the cardiac and vascular responses to hypertension, measurement of LV mass, geometry, and function, as well as effects of treatment. Published on behalf of the European Society of Cardiology. This article has been co-published in the Journal of the American Society of Echocardiography. All rights reserved. © The Author 2015.
    European Heart Journal Cardiovascular Imaging 06/2015; 16(6):577-605. DOI:10.1093/ehjci/jev076 · 4.11 Impact Factor
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    ABSTRACT: This study hypothesized that biomarkers of subclinical myocardial injury (high-sensitivity cardiac troponin T [hs-cTnT]) and hemodynamic stress (N-terminal pro-B-type natriuretic peptide [NT-proBNP]) would differentiate heart failure (HF) risk among older adults with left ventricular hypertrophy (LVH). The natural history of LVH, an important risk factor for HF, is heterogeneous. NT-proBNP and hs-cTnT were measured at baseline and after 2 to 3 years in older adults without prior HF or myocardial infarction in the CHS (Cardiovascular Health Study). LVH and left ventricular ejection fraction were determined by echocardiography. HF events were adjudicated over a median of 13.1 years and classified as preserved or reduced left ventricular ejection fraction (heart failure with preserved ejection fraction or heart failure with reduced ejection fraction [HFrEF]). Adjusted risk of HF by LVH and biomarker tertiles, and by LVH and longitudinal increase in each biomarker was estimated using Cox regression. Prevalence of LVH was 12.5% among 2,347 participants with complete measures. Adjusted risk of HF (N = 643 events) was approximately 3.8-fold higher among participants with LVH and in the highest biomarker tertile, compared with those with low biomarker levels without LVH (NT-proBNP, hazard ratio [HR]: 3.78; 95% confidence interval [CI]: 2.78 to 5.15 and hs-cTnT, HR: 3.86; 95% CI: 2.84 to 5.26). The adjusted risk of HFrEF was 7.8 times higher among those with the highest tertile of hs-cTnT and LVH (HR: 7.83; 95% CI: 4.43 to 13.83). Those with LVH and longitudinal increases in hs-cTnT or NT-proBNP were approximately 3-fold more likely to develop HF, primarily HFrEF, compared with those without LVH and with stable biomarkers. The combination of LVH with greater hs-cTnT or NT-proBNP levels, and their longitudinal increase, identifies older adults at highest risk for symptomatic HF, especially HFrEF. These biomarkers may characterize sub-phenotypes in the transition from LVH to HF and suggest modifiable targets for prevention. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
    05/2015; 3(6). DOI:10.1016/j.jchf.2014.12.018
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    ABSTRACT: As the U.S. population grows older, there is greater need to examine physical independence. Previous studies have assessed risk factors in relation to either disability or mortality, but an outcome that combines both is still needed. The Cardiovascular Health Study is a population-based, prospective study where participants underwent baseline echocardiogram, measurement of carotid intima-media thickness (IMT), and various biomarkers, then followed for up to 18 years. Years of able life (YAL) constituted the number of years the participant was able to perform all activities of daily living. Linear regression was used to model the relationship between selected measures and outcomes, adjusted for confounding variables. Among 4902 participants, mean age was 72.6±5.4 years, median YAL for males was 8.8 (interquartile range [IQR], 4.3 to 13.8) and 10.3 (IQR, 5.8 to 15.8) for females. Reductions in YAL in the fully adjusted model for females and males, respectively, were: -1.34 (95% confidence interval [CI], -2.18, -0.49) and -1.41 (95% CI, -2.03, -0.8) for abnormal left ventricular (LV) ejection fraction, -0.5 (95% CI, -0.78, -0.22) and -0.62 (95% CI, -0.87, -0.36) per SD increase in LV mass, -0.5 (95% CI, -0.7, -0.29) and -0.79 (95% CI, -0.99, -0.58) for IMT, -0.5 (95% CI, -0.64, -0.37) and -0.79 (95% CI, -0.94, -0.65) for N-terminal pro-brain natriuretic peptide, -1.08 (95% CI, -1.34, -0.83) and -0.73 (95% CI, -0.97, -0.5) for high-sensitivity troponin-T, and -0.26 (95% CI, -0.42, -0.09) and -0.23 (95% CI, -0.41, -0.05) for procollagen-III N-terminal propeptide. Most tested variables remained significant even after adjusting for incident cardiovascular (CV) disease. In this population-based cohort, variables obtained by CV imaging and biomarkers of inflammation, coagulation, atherosclerosis, myocardial injury and stress, and cardiac collagen turnover were associated with YAL, an important outcome that integrates physical ability and longevity in older persons. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.
    Journal of the American Heart Association 03/2015; 4(4). DOI:10.1161/JAHA.114.001745 · 4.31 Impact Factor

  • Journal of the American College of Cardiology 03/2015; 65(10):A1957. DOI:10.1016/S0735-1097(15)61957-X · 16.50 Impact Factor
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    ABSTRACT: Fibrosis has been implicated in a number of pathological, organ-based conditions of the liver, kidney, heart, and lungs. The objective of this study was to determine whether biomarkers of fibrosis are associated with vascular disease in the large and/or small vessels. We evaluated the associations of two circulating biomarkers of fibrosis, transforming growth factor-β (TGF-β) and procollagen type III N-terminal propeptide (PIIINP), with incident peripheral artery disease (PAD) and subclinical macrovascular (carotid intima-media thickness, flow-mediated vasodilation, ankle-brachial index, retinal vein diameter), and microvascular (retinal artery diameter and retinopathy) disease among older adults in the Cardiovascular Health Study. We measured TGF-β and PIIINP from samples collected in 1996 and ascertained clinical PAD through 2011. Measurements of large and small vessels were collected between 1996 and 1998. After adjustment for sociodemographic, clinical, and biochemical risk factors, TGF-β was associated with incident PAD (hazard ratio [HR] = 1.36 per doubling of TGF-β, 95% confidence interval [CI] = 1.04, 1.78) and retinal venular diameter (1.63 μm per doubling of TGF-β, CI = 0.23, 3.02). PIIINP was not associated with incident PAD, but was associated with carotid intima-media thickness (0.102 mm per doubling of PIIINP, CI = 0.029, 0.174) and impaired brachial artery reactivity (-0.20% change per doubling of PIIINP, CI = -0.39, -0.02). Neither TGF-β nor PIIINP were associated with retinal arteriolar diameter or retinopathy. Serum concentrations of fibrosis-related biomarkers were associated with several measures of large vessel disease, including incident PAD, but not with small vessel disease. Fibrosis may contribute to large vessel atherosclerosis in older adults. Copyright © 2015. Published by Elsevier Ireland Ltd.
    Atherosclerosis 02/2015; 239(2):539-546. DOI:10.1016/j.atherosclerosis.2015.02.020 · 3.99 Impact Factor
  • Bruce M Psaty · Sanjiv J Shah · John Gottdiener ·

    Circulation 02/2015; 131(6):e343-e343. DOI:10.1161/CIRCULATIONAHA.114.012243 · 14.43 Impact Factor
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    ABSTRACT: Background HIV infection is associated with increased risk of cardiovascular disease (CVD) in men. Whether HIV is an independent risk factor for CVD in women has not yet been established. Methods and Results We analyzed data from the Veterans Aging Cohort Study on 2187 women (32% HIV infected [HIV+]) who were free of CVD at baseline. Participants were followed from their first clinical encounter on or after April 01, 2003 until a CVD event, death, or the last follow‐up date (December 31, 2009). The primary outcome was CVD (acute myocardial infarction [AMI], unstable angina, ischemic stroke, and heart failure). CVD events were defined using clinical data, International Classification of Diseases, Ninth Revision, Clinical Modification codes, and/or death certificate data. We used Cox proportional hazards models to assess the association between HIV and incident CVD, adjusting for age, race/ethnicity, lipids, smoking, blood pressure, diabetes, renal disease, obesity, hepatitis C, and substance use/abuse. Median follow‐up time was 6.0 years. Mean age at baseline of HIV+ and HIV uninfected (HIV−) women was 44.0 versus 43.2 years (P<0.05). Median time to CVD event was 3.1 versus 3.7 years (P=0.11). There were 86 incident CVD events (53%, HIV+): AMI, 13%; unstable angina, 8%; ischemic stroke, 22%; and heart failure, 57%. Incident CVD/1000 person‐years was significantly higher among HIV+ (13.5; 95% confidence interval [CI]=10.1, 18.1) than HIV− women (5.3; 95% CI=3.9, 7.3; P<0.001). HIV+ women had an increased risk of CVD, compared to HIV− (hazard ratio=2.8; 95% CI=1.7, 4.6; P<0.001). Conclusions HIV is associated with an increased risk of CVD in women.
    Journal of the American Heart Association 09/2014; 3(5). DOI:10.1161/JAHA.114.001035 · 4.31 Impact Factor
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    ABSTRACT: Aims B-type natriuretic peptide (BNP) and C-reactive protein (CRP) predict atrial fibrillation (AF) risk. However, their risk stratification abilities in the broad community remain uncertain. We sought to improve risk stratification for AF using biomarker information. Methods and results We ascertained AF incidence in 18 556 Whites and African Americans from the Atherosclerosis Risk in Communities Study (ARIC, n=10 675), Cardiovascular Health Study (CHS, n=5043), and Framingham Heart Study (FHS, n = 2838), followed for 5 years (prediction horizon). We added BNP (ARIC/CHS: N-terminal pro-B-type natriuretic peptide; FHS: BNP), CRP, or both to a previously reported AF risk score, and assessed model calibration and predictive ability [C-statistic, integrated discrimination improvement (IDI), and net reclassification improvement (NRI)]. We replicated models in two independent European cohorts: Age, Gene/Environment Susceptibility Reykjavik Study (AGES), n=4467; Rotterdam Study (RS), n=3203. B-type natriuretic peptide and CRP were significantly associated with AF incidence (n=1186): hazard ratio per 1-SD ln-transformed biomarker 1.66 [95% confidence interval (CI), 1.56-1.76], P < 0.0001 and 1.18 (95% CI, 1.11-1.25), P < 0.0001, respectively. Model calibration was sufficient (BNP, chi(2)=17.0; CRP, chi(2)=10.5; BNP and CRP, chi(2)=13.1). B-type natriuretic peptide improved the C-statistic from 0.765 to 0.790, yielded an IDI of 0.027 (95% CI, 0.022-0.032), a relative IDI of 41.5%, and a continuous NRI of 0.389 (95% CI, 0.322-0.455). The predictive ability of CRP was limited (C-statistic increment 0.003). B-type natriuretic peptide consistently improved prediction in AGES and RS. Conclusion B-type natriuretic peptide, not CRP, substantially improved AF risk prediction beyond clinical factors in an independently replicated, heterogeneous population. B-type natriuretic peptide may serve as a benchmark to evaluate novel putative AF risk biomarkers.
    Europace 07/2014; 16(10). DOI:10.1093/europace/euu175 · 3.67 Impact Factor
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    ABSTRACT: Background: Fibrotic changes in the heart and arteries have been implicated in a diverse range of cardiovascular diseases (CVD), but whether circulating biomarkers that reflect fibrosis are associated with CVD is unknown. Methods and results: We determined the associations of 2 biomarkers of fibrosis, transforming growth factor- β (TGF-β), and procollagen type III N-terminal propeptide (PIIINP), with incident heart failure, myocardial infarction, and stroke among community-living older adults in the Cardiovascular Health Study. We measured circulating TGF-β (n=1371) and PIIINP (n=2568) from plasma samples collected in 1996 and ascertained events through 2010. Given TGF-β's pleiotropic effects on inflammation and fibrogenesis, we investigated potential effect modification by C-reactive protein in secondary analyses. After adjustment for sociodemographic, clinical, and biochemical risk factors, PIIINP was associated with total CVD (hazard ratio [HR] per SD=1.07; 95% confidence interval [CI], 1.01-1.14) and heart failure (HR per SD=1.08; CI, 1.01-1.16) but not myocardial infarction or stroke. TGF-β was not associated with any CVD outcomes in the full cohort but was associated with total CVD (HR per SD=1.16; CI, 1.02-1.31), heart failure (HR per SD=1.16; CI, 1.01-1.34), and stroke (HR per SD=1.20; CI, 1.01-1.42) among individuals with C-reactive protein above the median, 2.3 mg/L (P interaction <0.05). Conclusions: Our findings provide large-scale, prospective evidence that circulating biomarkers of fibrosis, measured in community-living individuals late in life, are associated with CVD. Further research on whether TGF-β has a stronger fibrogenic effect in the setting of inflammation is warranted.
    Circulation Arrhythmia and Electrophysiology 06/2014; 7(4). DOI:10.1161/CIRCEP.114.001610 · 4.51 Impact Factor
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    ABSTRACT: Fibrosis has been implicated in diverse diseases of the liver, kidney, lungs, and heart, but its importance as a risk factor for mortality remains unconfirmed. We determined the prospective associations of 2 complementary biomarkers of fibrosis, transforming growth factor-β (TGF-β) and procollagen type III N-terminal propeptide (PIIINP), with total and cause-specific mortality risks among community-living older adults in the Cardiovascular Health Study (1996-2010). We measured circulating TGF-β and PIIINP levels in plasma samples collected in 1996 and ascertained the number of deaths through 2010. Both TGF-β and PIIINP were associated with elevated risks of total and pulmonary mortality after adjustment for sociodemographic, clinical, and biochemical risk factors. For total mortality, the hazard ratios per doubling of TGF-β and PIIINP were 1.09 (95% confidence interval (CI): 1.01, 1.17; P = 0.02) and 1.14 (CI: 1.03, 1.27; P = 0.01), respectively. The corresponding hazard ratios for pulmonary mortality were 1.27 (CI: 1.01, 1.60; P = 0.04) for TGF-β and 1.52 (CI: 1.11, 2.10; P = 0.01) for PIIINP. Associations of TGF-β and PIIINP with total and pulmonary mortality were strongest among individuals with higher C-reactive protein concentrations (P for interaction < 0.05). Our findings provide some of the first large-scale prospective evidence that circulating biomarkers of fibrosis measured late in life are associated with death.
    American journal of epidemiology 04/2014; 179(11). DOI:10.1093/aje/kwu067 · 5.23 Impact Factor
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    Journal of the American College of Cardiology 04/2014; 63(12):A768. DOI:10.1016/S0735-1097(14)60768-3 · 16.50 Impact Factor

  • Journal of the American College of Cardiology 04/2014; 63(12):A738. DOI:10.1016/S0735-1097(14)60738-5 · 16.50 Impact Factor

Publication Stats

19k Citations
2,739.79 Total Impact Points


  • 2015
    • University of Maryland, College Park
      CGS, Maryland, United States
  • 2006-2015
    • University of Maryland Medical Center
      • • Division of Cardiology
      • • Department of Medicine
      Baltimore, Maryland, United States
    • Duke University
      Durham, North Carolina, United States
  • 1990-2015
    • University of Maryland, Baltimore
      • • Department of Medicine
      • • Division of Cardiology
      Baltimore, Maryland, United States
  • 2011
    • University of California, Irvine
      • Division of Cardiology
      Irvine, California, United States
  • 2007
    • Columbia University
      • College of Physicians and Surgeons
      New York, New York, United States
  • 1993-2007
    • Uniformed Services University of the Health Sciences
      • Department of Medical & Clinical Psychology
      Maryland, United States
  • 2000-2006
    • St. Francis Hospital
      Roslyn, New York, United States
  • 1999-2005
    • Saint Francis Hospital
      Tulsa, Oklahoma, United States
    • University of Pittsburgh
      Pittsburgh, Pennsylvania, United States
  • 2004
    • Johns Hopkins University
      Baltimore, Maryland, United States
    • University of Washington Seattle
      Seattle, Washington, United States
    • University of California, Davis
      • School of Medicine
      Davis, CA, United States
  • 1982-2003
    • Georgetown University
      • Division of Cardiology
      Washington, Washington, D.C., United States
  • 2002
    • William Penn University
      Filadelfia, Pennsylvania, United States
  • 2001
    • Johns Hopkins Medicine
      Baltimore, Maryland, United States
  • 1982-1991
    • Washington DC VA Medical Center
      Washington, Washington, D.C., United States
  • 1978-1990
    • National Heart, Lung, and Blood Institute
      • Hematology Branch
      Maryland, United States
  • 1982-1984
    • American University Washington D.C.
      Washington, Washington, D.C., United States
  • 1983
    • Tufts Medical Center
      Boston, Massachusetts, United States
  • 1978-1981
    • National Institutes of Health
      베서스다, Maryland, United States
  • 1980
    • NCI-Frederick
      Фредерик, Maryland, United States
  • 1979
    • George Washington University
      • Department of Medicine
      Washington, Washington, D.C., United States