John S Gottdiener

University of Maryland Medical Center, Baltimore, Maryland, United States

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Publications (275)2013.36 Total impact

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    ABSTRACT: 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.
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    ABSTRACT: -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.
    Circulation Arrhythmia and Electrophysiology 06/2014; · 5.42 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; · 4.98 Impact Factor
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    ABSTRACT: Atrial fibrillation (AF) prediction models have unclear clinical utility given the absence of AF prevention therapies and the immutability of many risk factors. Premature atrial contractions (PACs) play a critical role in AF pathogenesis and may be modifiable. To investigate whether PAC count improves model performance for AF risk. Prospective cohort study. 4 U.S. communities. A random subset of 1260 adults without prevalent AF enrolled in the Cardiovascular Health Study between 1989 and 1990. The PAC count was quantified by 24-hour electrocardiography. Participants were followed for the diagnosis of incident AF or death. The Framingham AF risk algorithm was used as the comparator prediction model. In adjusted analyses, doubling the hourly PAC count was associated with a significant increase in AF risk (hazard ratio, 1.17 [95% CI, 1.13 to 1.22]; P < 0.001) and overall mortality (hazard ratio, 1.06 [CI, 1.03 to 1.09]; P < 0.001). Compared with the Framingham model, PAC count alone resulted in similar AF risk discrimination at 5 and 10 years of follow-up and superior risk discrimination at 15 years. The addition of PAC count to the Framingham model resulted in significant 10-year AF risk discrimination improvement (c-statistic, 0.65 vs. 0.72; P < 0.001), net reclassification improvement (23.2% [CI, 12.8% to 33.6%]; P < 0.001), and integrated discrimination improvement (5.6% [CI, 4.2% to 7.0%]; P < 0.001). The specificity for predicting AF at 15 years exceeded 90% for PAC counts more than 32 beats/h. This study does not establish a causal link between PACs and AF. The addition of PAC count to a validated AF risk algorithm provides superior AF risk discrimination and significantly improves risk reclassification. Further study is needed to determine whether PAC modification can prospectively reduce AF risk. American Heart Association, Joseph Drown Foundation, and National Institutes of Health.
    Annals of internal medicine 12/2013; 159(11):721-8. · 16.10 Impact Factor
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    ABSTRACT: In chronic kidney disease (CKD), high FGF23 concentrations are associated with left ventricular hypertrophy (LVH), cardiovascular events, and death. The associations of FGF23 with left ventricular mass (LVM) and LVH in the general population and the influence of CKD remains uncertain. C-terminal plasma FGF23 concentrations were measured, and LVM and LVH evaluated by echocardiogram among 2255 individuals ≥65 years in the Cardiovascular Health Study. Linear regression analysis adjusting for demographics, cardiovascular, and kidney related risk factors examined the associations of FGF23 concentrations with LVM. Analyses were stratified by CKD status and adjusted linear and logistic regression analysis explored the associations of FGF23 with LVM and LVH. Among the entire cohort, higher FGF23 concentrations were associated with greater LVM in adjusted analyses (β = 6.71 [95% CI 4.35-9.01] g per doubling of FGF23). 32% (n = 624) had CKD (eGFR <60 mL/min/1.73 m(2) and/or urine albumin-to-creatinine ratio >30 mg/g). Associations were stronger among participants with CKD (p interaction = 0.006): LVM β = 9.71 [95% CI 5.86-13.56] g per doubling of FGF23 compared to those without CKD (β = 3.44 [95% CI 0.77, 6.11] g per doubling of FGF23). While there was no significant interaction between FGF23 and CKD for LVH (p interaction = 0.25), the OR (1.46 95% CI [1.20-1.77]) in the CKD group was statistically significant and of larger magnitude than the OR for in the no CKD group (1.12 [95% CI 0.97-1.48]). In a large cohort of older community-dwelling adults, higher FGF23 concentrations were associated with greater LVM and LVH with stronger relationships in participants with CKD.
    Atherosclerosis 11/2013; 231(1):114-119. · 3.71 Impact Factor
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    ABSTRACT: Adiponectin exhibits cardioprotective properties in experimental studies, but elevated levels have been linked to increased mortality in older adults and patients with chronic heart failure (HF). The adipokine's association with new-onset HF remains less well defined. The aim of this study was to investigate the associations of total and high-molecular weight (HMW) adiponectin with incident HF (n = 780) and, in a subset, echocardiographic parameters in a community-based cohort of adults aged ≥65 years. Total and HMW adiponectin were measured in 3,228 subjects without prevalent HF, atrial fibrillation or CVD. The relations of total and HMW adiponectin with HF were nonlinear, with significant associations observed only for concentrations greater than the median (12.4 and 6.2 mg/L, respectively). After adjustment for potential confounders, the hazard ratios per SD increment in total adiponectin were 0.93 (95% confidence interval 0.72 to 1.21) for concentrations less than the median and 1.25 (95% confidence interval 1.14 to 1.38) higher than the median. There was a suggestion of effect modification by body mass index, whereby the association appeared strongest in participants with lower body mass indexes. Consistent with the HF findings, higher adiponectin tended to be associated with left ventricular systolic dysfunction and left atrial enlargement. Results were similar for HMW adiponectin. In conclusion, total and HMW adiponectin showed comparable relations with incident HF in this older cohort, with a threshold effect of increasing risk occurring at their median concentrations. High levels of adiponectin may mark or mediate age-related processes that lead to HF in older adults.
    The American journal of cardiology 10/2013; · 3.58 Impact Factor
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    ABSTRACT: -Although plasma free fatty acid (FFA) concentrations have been associated with lipotoxicity, apoptosis, and risk of diabetes and coronary heart disease, it is unclear whether FFA levels are associated with heart failure (HF). -To test the hypothesis that plasma concentration of FFA is positively associated with incident HF, we prospectively analyzed data on 4248 men and women free of HF at baseline and aged 65+ years from the Cardiovascular Health Study. FFA concentration was measured in duplicate by the Wako enzymatic method. Incident HF was validated by a centralized Events Committee. We used Cox proportional hazards to estimate the hazard ratio of HF per standard deviation (SD) of FFA. During a median follow up of 10.5 y, 1,286 new cases of HF occurred. In a multivariable model adjusting for clinic site, comorbidity, demographic, anthropometric, and lifestyle factors, each SD (0.2 mEq/L) higher plasma FFA was associated with 12% (95% CI: 6% to 19%) higher risk of HF. Controlling for time-varying diabetes and coronary heart disease did not change the results [HR per SD: 1.16 (95% CI: 1.09-1.23)]. -A single measure of plasma FFA obtained later in life is associated with a higher risk of HF in older adults. Additional studies are needed to explore biologic mechanisms by which FFA may influence the risk of HF and determine whether FFA could serve as a novel pharmacological target for HF prevention.
    Circulation Heart Failure 08/2013; · 6.68 Impact Factor
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    ABSTRACT: To study the association between markers of cardiomyocyte injury in ambulatory subjects and sudden cardiac death (SCD). The pathophysiology of SCD is complex but is believed to be associated with an abnormal cardiac substrate in most cases. The association between biomarkers of cardiomyocyte injury in ambulatory subjects and SCD has not been investigated. Levels of cardiac Troponin T, a biomarker of cardiomyocyte injury, were measured by a highly sensitive assay (hsTnT) in 4431 ambulatory participants in the Cardiovascular Health Study, a longitudinal community-based prospective cohort study. Serial measures were obtained in 3089 subjects. All deaths, including SCD, were adjudicated by a central events committee. Over a median follow-up of 13.1 years, 246 participants had SCD. Baseline levels of hsTnT were significantly associated with SCD [Hazard ratio (HR) for +1Log(hsTnT) 2.04, 95% confidence interval (CI) 1.78-2.34]. This association persisted in covariate-adjusted Cox analyses accounting for baseline risk factors (HR 1.30, 95%CI 1.05-1.62), as well as for incident heart failure and myocardial infarction (HR 1.26, 95%CI 1.01-1.57). The population was also categorized into 3 groups based on baseline hsTnT levels and SCD risk [Fully-adjusted HRs 1.89 vs. 1.55 vs. 1 (reference group) for hsTnT≥12.10 vs. 5.01-12.09 vs. ≤5.00 pg/mL, respectively; Ptrend=0.005]. On serial measurements, change in hsTnT levels was also associated with SCD risk (Fully-adjusted HR for +1pg/ml per year increase from baseline 1.03, 95%CI 1.01-1.06). The findings suggest an association between cardiomyocyte injury in ambulatory subjects and SCD risk beyond that of traditional risk factors.
    Journal of the American College of Cardiology 08/2013; · 15.34 Impact Factor
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    ABSTRACT: Objectives This study sought to determine whether the combined trajectories of cardiac biomarkers identify those older adults with initial low levels who have an increased risk for structural heart disease, incident heart failure (HF), and cardiovascular (CV) death. Background Initial low levels of high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) identify older adults at lower risk for CV events. Methods We performed an observational study among older adults without prevalent HF in the CHS (Cardiovascular Health Study). NT-proBNP and hs-cTnT were measured at baseline and after 2 to 3 years. In those with low baseline levels, a significant increase was defined as cardiac troponin T (cTnT) >50% and NT-proBNP >25% increase to >190 pg/ml. Left ventricular ejection fraction and left ventricular mass were measured by echocardiography at baseline and 5 years. Cox regression was used to estimate the association of change in biomarkers with HF and CV mortality. Results Among 2,008 participants with initially low biomarker concentrations, significant increases occurred in 14.8% for cTnT only, 13.2% for NT-proBNP only, and 6.1% for both. After 10 years, cumulative HF incidence was 50.4% versus 12.2% among those with both biomarkers versus neither biomarker increased. The adjusted relative risk comparing those with increases in both biomarkers versus neither biomarker was 3.56 for incident HF (95% confidence interval: 2.56 to 4.97) and 2.98 for CV mortality (95% confidence interval: 2.98 to 4.26). Among 1,340 participants with serial echocardiography, the frequency of new abnormal left ventricular ejection fraction was 11.8% versus 4% for those with increases in both biomarkers versus neither biomarker (p = 0.007). Conclusions Among older adults without HF with initially low cTnT and NT-proBNP, the long-term trajectory of both biomarkers predicts systolic dysfunction, incident HF, and CV death.
    JACC: Heart Failure. 08/2013; 1(4):353–360.
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    ABSTRACT: To study the association between inflammation and sudden cardiac death (SCD) in a community-based population of older adults. Inflammation is linked to adverse cardiovascular events but its association with SCD has been controversial. Older subjects, who are at particular risk for SCD, were underrepresented in previous studies addressing this issue. In the Cardiovascular Health Study, 5806 and 5382 participants had measurements of C-reactive protein (CRP) and Interleukin-6 (IL6), respectively; and were followed for up to 17 years. SCD risk as a function of baseline IL-6 and CRP was assessed in the overall population and a group of participants without known prevalent cardiac disease. In univariate analyses, both IL-6 [Hazard ratio (HR) 1.79 for 1+ log IL-6, 95% confidence interval (CI) 1.50-2.13; 5(th) vs. 1(st) quintile HR 3.36, 95%CI 2.24-5.05] and CRP (HR 1.31 for 1+ log CRP, 95%CI 1.18-1.45; 5(th) vs. 1(st) quintile HR 2.00, 95%CI 1.40-2.87) were associated with SCD risk. In covariate-adjusted analyses, accounting for baseline risk factors, incident myocardial infarction and heart failure, the association with SCD risk persisted for IL-6 (HR 1.26 for 1+ log IL-6, 95%CI 1.02-1.56, 5(th) vs. 1(st) quintile HR 1.63, 95%CI 1.03-2.56), but was significantly attenuated for CRP (HR 1.13 for 1+ log CRP, 95%CI 1.00-1.28, 5(th) vs. 1(st) quintile HR 1.34, 95%CI 0.88-2.05). Similar findings were observed in participants without prevalent cardiac disease. Greater burden of inflammation, assessed by IL-6 levels, is associated with SCD risk beyond traditional risk factors, incident myocardial infarction and heart failure.
    Heart rhythm: the official journal of the Heart Rhythm Society 07/2013; · 4.56 Impact Factor
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    ABSTRACT: Tools for the prediction of atrial fibrillation (AF) may identify high-risk individuals more likely to benefit from preventive interventions and serve as a benchmark to test novel putative risk factors. Individual-level data from 3 large cohorts in the United States (Atherosclerosis Risk in Communities [ARIC] study, the Cardiovascular Health Study [CHS], and the Framingham Heart Study [FHS]), including 18 556 men and women aged 46 to 94 years (19% African Americans, 81% whites) were pooled to derive predictive models for AF using clinical variables. Validation of the derived models was performed in 7672 participants from the Age, Gene and Environment-Reykjavik study (AGES) and the Rotterdam Study (RS). The analysis included 1186 incident AF cases in the derivation cohorts and 585 in the validation cohorts. A simple 5-year predictive model including the variables age, race, height, weight, systolic and diastolic blood pressure, current smoking, use of antihypertensive medication, diabetes, and history of myocardial infarction and heart failure had good discrimination (C-statistic, 0.765; 95% CI, 0.748 to 0.781). Addition of variables from the electrocardiogram did not improve the overall model discrimination (C-statistic, 0.767; 95% CI, 0.750 to 0.783; categorical net reclassification improvement, -0.0032; 95% CI, -0.0178 to 0.0113). In the validation cohorts, discrimination was acceptable (AGES C-statistic, 0.664; 95% CI, 0.632 to 0.697 and RS C-statistic, 0.705; 95% CI, 0.664 to 0.747) and calibration was adequate. A risk model including variables readily available in primary care settings adequately predicted AF in diverse populations from the United States and Europe.
    Journal of the American Heart Association. 01/2013; 2(2):e000102.
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    ABSTRACT: AimTo examine the association of plasma fatty acid-binding protein 4 (FABP4) with incident heart failure. METHODS AND RESULTS: In a prospective study of 4179 participants from the Cardiovascular Health Study, we measured plasma FABP4 on blood specimens collected between 1992 and 1993. Incident heart failure was adjudicated by an endpoint committee and we used a Cox proportional hazards model to calculate hazard ratios (HRs) of heart failure. The average age at baseline was 75 years. During a median follow-up of 10.7 years, 1182 cases of incident heart failure occurred. We observed a positive association between FABP4 and heart failure in the minimally adjusted models [HR 1.32, 95% confidence interval (CI) 1.25-1.38 per 1 SD higher FABP4] that was attenuated upon adjustment for potential confounders, mostly kidney function and body mass index (corresponding HR 1.09, 95% CI 1.01-1.17). In a subsample of heart failure cases with available data on LV systolic function, FABP4 was not associated with heart failure with or without preserved LV systolic function. Exclusion of people with unintentional weight loss and self-reported fair/poor health status did not alter the conclusion. CONCLUSION: An elevated plasma concentration of FABP4 was associated with a modestly higher risk of heart failure in older adults in the USA after adjustment for confounding factors.
    European Journal of Heart Failure 12/2012; · 5.25 Impact Factor
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    ABSTRACT: Vitamin D and parathyroid hormone (PTH) may affect cardiovascular health in patients with kidney disease and in the general population. The aim of this study was to investigate associations of serum 25-hydroxyvitamin D (25(OH)D) and PTH concentrations with a comprehensive set of biochemical, electrocardiographic, and echocardiographic measurements of cardiac structure and function in the Cardiovascular Health Study. A total of 2,312 subjects who were free of cardiovascular disease at baseline were studied. Serum 25(OH)D and intact PTH concentrations were measured using mass spectrometry and a 2-site immunoassay. Outcomes were N-terminal pro-B-type natriuretic peptide, cardiac troponin T, electrocardiographic measures of conduction, and echocardiographic measures of left ventricular mass and diastolic dysfunction. At baseline, subjects had a mean age of 73.9 ± 4.9 years, 69.7% were women, and 21% had chronic kidney disease (glomerular filtration rate <60 ml/min). Mean 25(OH)D was 25.2 ± 10.2 ng/ml, and median PTH was 51 pg/ml (range 39 to 65). After adjustment, 25(OH)D was not associated with any of the biochemical, conduction, or echocardiographic outcomes. Serum PTH levels ≥65 pg/ml were associated with greater N-terminal pro-B-type natriuretic peptide, cardiac troponin T, and left ventricular mass in patients with chronic kidney disease. The regression coefficients were: 120 pg/ml (95% confidence interval 36.1 to 204), 5.2 pg/ml (95% confidence interval 3.0 to 7.4), and 17 g (95% confidence interval 6.2 to 27.8) (p <0.001). In subjects with normal kidney function, PTH was not associated with the outcomes. In conclusion, in older adults with chronic kidney disease, PTH excess is associated with higher N-terminal pro-B-type natriuretic peptide, cardiac troponin T, and left ventricular mass. These findings suggest a role for PTH in cardiovascular health and the prevention of cardiac diseases.
    The American journal of cardiology 11/2012; · 3.58 Impact Factor
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    ABSTRACT: Context:Adiponectin is atheroprotective in the laboratory, but prospective studies have shown opposite associations with cardiovascular disease (CVD) in healthy middle-aged populations (protective) and older cohorts (adverse). Whether this relates to different proportions of high-molecular-weight (HMW) adiponectin is unknown.Objective:The aim of the study was to test the hypothesis that total adiponectin is directly associated, but HMW adiponectin is inversely related, with CVD in older adults.Design, Setting, and Participants:We evaluated 3290 participants free of prevalent CVD in a longitudinal cohort study of U.S. adults aged 65 yr and older.Main Outcome Measures:We measured incident CVD (n = 1291), comprising coronary heart disease and ischemic stroke.Results:Total and HMW adiponectin were tightly correlated (r = 0.94). Cubic splines adjusted for potential confounders revealed that the associations of total and HMW adiponectin with CVD were U-shaped, with inflection points of 20 and 10 mg/liter, respectively. After controlling for potential confounding, levels of total and HMW adiponectin below these cutpoints tended to be inversely associated with incident CVD, driven by their significant or near-significant relations with coronary heart disease [hazard ratio (HR), 0.85 per sd increase; 95% confidence interval (CI), 0.75-96; and HR, 0.87; 95% CI, 0.75-1.01, respectively]. These associations were abrogated by additional inclusion of putative metabolic intermediates. Above these cutpoints, however, both total and HMW adiponectin were significantly directly associated with CVD after adjustment for confounders and, particularly, mediators (HR, 1.20 per sd increase; 95% CI, 1.06-1.35; and HR, 1.12; 95% CI, 1.02-1.24, respectively).Conclusion:In community-living elders, total and HMW adiponectin showed similar U-shaped relationships with CVD. The inverse relation in the lower range, but not the direct association at the higher end, disappeared after inclusion of putative intermediates, suggesting that high levels may reflect adverse processes separate from adiponectin's beneficial glycometabolic properties.
    The Journal of Clinical Endocrinology and Metabolism 11/2012; · 6.31 Impact Factor
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    ABSTRACT: OBJECTIVES: The aim of this study was to evaluate the association between physical activity and changes in levels of highly sensitive troponin T (cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP), and the subsequent risk of the development of heart failure (HF) in community-dwelling older adults. BACKGROUND: Higher baseline levels of cTnT and NT-proBNP and increases over time correlate with the risk of HF in older adults. Factors modifying these levels have not been identified. METHODS: NT-proBNP and cTnT were measured at baseline and 2 to 3 years later in adults 65 years of age and older free of HF participating in the Cardiovascular Health Study. Self-reported physical activity and walking pace were combined into a composite score. An increase was prespecified for NT-proBNP as a >25% increment from baseline to ≥190 pg/ml and for cTnT as a >50% increment from baseline in participants with detectable levels (≥3 pg/ml). RESULTS: A total of 2,933 participants free of HF had NT-proBNP and cTnT measured at both time points. The probability of an increase in biomarker concentrations between baseline and follow-up visits was inversely related to the physical activity score. Compared with participants with the lowest score, those with the highest score had an odds ratio of 0.50 (95% confidence interval: 0.33 to 0.77) for an increase in NT-proBNP and an odds ratio of 0.30 (95% confidence interval: 0.16 to 0.55) for an increase in cTnT, after adjusting for comorbidities and baseline levels. A higher activity score associated with a lower long-term incidence of HF. Moreover, at each level of activity, an increase in either biomarker still identified those at higher risk. CONCLUSIONS: These findings suggest that moderate physical activity has protective effects on early heart failure phenotypes, preventing cardiac injury and neurohormonal activation.
    Journal of the American College of Cardiology 11/2012; · 15.34 Impact Factor
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    ABSTRACT: AimsAtrial fibrillation (AF) is the most common sustained arrhythmia. Increased body size has been associated with AF, but the relationship is not well understood. In this study, we examined the effect of increased height on the risk of AF and explore potential mediators and implications for clinical practice.Methods and resultsWe examined data from 5860 individuals taking part in the Cardiovascular Health Study, a cohort study of older US adults followed for a median of 13.6 (women) and 10.3 years (men). Multivariate linear models and age-stratified Cox proportional hazards and risk models were used, with focus on the effect of height on both prevalent and incident AF. Among 684 (22.6%) and 568 (27.1%) incident cases in women and men, respectively, greater height was significantly associated with AF risk [hazard ratio (HR)(women) per 10 cm 1.32, confidence interval (CI) 1.16-1.50, P < 0.0001; HR(men) per 10 cm 1.26, CI 1.11-1.44, P < 0.0001]. The association was such that the incremental risk from sex was completely attenuated by the inclusion of height (for men, HR 1.48, CI 1.32-1.65, without height, and HR 0.94, CI 0.85-1.20, with height included). Inclusion of height in the Framingham model for incident AF improved discrimination. In sequential models, however, we found minimal attenuation of the risk estimates for AF with adjustment for left ventricular (LV) mass and left atrial (LA) dimension. The associations of LA and LV size measurements with AF risk were weakened when indexed to height.Conclusion Independent from sex, increased height is significantly associated with the risk of AF.
    European Heart Journal 09/2012; · 14.72 Impact Factor
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    ABSTRACT: To determine the relationship between heart rate response during low-grade physical exertion (6-min walk) with mortality and adverse cardiovascular outcomes in the elderly. Participants in the Cardiovascular Health Study who completed a 6-min walk test were included. We used delta heart rate (difference between postwalk heart rate and resting heart rate) as a measure of chronotropic response and examined its association with (1) all-cause mortality and (2) incident coronary heart disease event, using multivariable Cox regression models. We included 2,224 participants (mean age 77 ± 4 years; 60% women; 85% white). The average delta heart rate was 26 beats/min. Participants in the lowest tertile of delta heart rate (<20 beats/min) had higher risk-adjusted mortality [hazard ratio (HR) 1.18, 95% confidence interval (CI) 1.00-1.40] and incident coronary heart disease (HR 1.37, 95% CI 1.05-1.78) compared to subjects in the highest tertile (≥30 beats/min), with a significant linear trend across tertiles (p for trend <0.05 for both outcomes). This relationship was not significant after adjustment for distance walked. Impaired chronotropic response during a 6-min walk test was associated with an increased risk of mortality and incident coronary heart disease among the elderly. This association was attenuated after adjusting for distance walked.
    Cardiology 06/2012; 122(2):69-75. · 2.04 Impact Factor
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    ABSTRACT: BACKGROUND: Repeated myocardial microinjuries lead to collagen deposition and fibrosis, thereby increasing the risk of clinical heart failure. Little is known about the longitudinal association between increases in myocardial injury and the biology of collagen synthesis and deposition. METHODS AND RESULTS: Repeated measures of highly sensitive cardiac troponin T (cTnT) were obtained in participants of the Cardiovascular Health Study (N=353; mean age, 74±6 years; 52% women) at baseline and at 3 years follow-up. Biomarkers of collagen metabolism were obtained at follow-up and included carboxyterminal propeptide of procollagen type I, carboxyterminal telopeptide of type I collagen, and aminoterminal propeptide of procollagen III. Multivariable linear regression analyses were used to examine the association between baseline cTnT and changes in cTnT with collagen metabolism markers at follow-up adjusting for demographics, heart failure status, and cardiovascular risk factors. Results indicated that cTnT increases over 3-years were significantly associated with higher levels of carboxyterminal telopeptide of type I collagen (β=0.22, P<0.001) and aminoterminal propeptide of procollagen III (β=0.12, P=0.035) at follow-up when adjusting for demographic, clinical, and biochemical covariates including baseline cTnT. These associations were stronger in patients with heart failure than in control subjects. Conclusions- Increases in myocardial microinjury measured by changes in cTnT adversely affect markers of collagen metabolism. These findings are important to the biology of myocardial fibrosis and tissue repair. Serial evaluation of cTnT combined with collagen metabolism markers may further elucidate the pathophysiology of heart failure.
    Circulation Heart Failure 06/2012; 5(4):406-13. · 6.68 Impact Factor
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    JACC. Cardiovascular imaging 05/2012; 5(5):572-3. · 14.29 Impact Factor
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    ABSTRACT: This study sought to examine the potential utility of echocardiography and N-terminal pro-B-type natriuretic peptide (NT-proBNP) for heart failure (HF) risk stratification in concert with a validated clinical HF risk score in older adults. Without clinical guidance, echocardiography and natriuretic peptides have suboptimal test characteristics for population-wide HF risk stratification. However, the value of these tests has not been examined in concert with a clinical HF risk score. We evaluated the improvement in 5-year HF risk prediction offered by adding an echocardiographic score and/or NT-proBNP levels to the clinical Health Aging and Body Composition (ABC) HF risk score (base model) in 3,752 participants of the CHS (Cardiovascular Health Study) (age 72.6 ± 5.4 years; 40.8% men; 86.5% white). The echocardiographic score was derived as the weighted sum of independent echocardiographic predictors of HF. We assessed changes in Bayesian information criterion (BIC), C index, integrated discrimination improvement (IDI), and net reclassification improvement (NRI). We examined also the weighted NRI across baseline HF risk categories under multiple scenarios of event versus nonevent weighting. Reduced left ventricular ejection fraction, abnormal E/A ratio, enlarged left atrium, and increased left ventricular mass were independent echocardiographic predictors of HF. Adding the echocardiographic score and NT-proBNP levels to the clinical model improved BIC (echocardiography: -43, NT-proBNP: -64.1, combined: -68.9; all p < 0.001) and C index (baseline: 0.746; echocardiography: +0.031, NT-proBNP: +0.027, combined: +0.043; all p < 0.01), and yielded robust IDI (echocardiography: 43.3%, NT-proBNP: 42.2%, combined: 61.7%; all p < 0.001), and NRI (based on Health ABC HF risk groups; echocardiography: 11.3%; NT-proBNP: 10.6%, combined: 16.3%; all p < 0.01). Participants at intermediate risk by the clinical model (5% to 20% 5-yr HF risk; 35.7% of the cohort) derived the most reclassification benefit. Echocardiography yielded modest reclassification when used sequentially after NT-proBNP. In older adults, echocardiography and NT-proBNP offer significant HF risk reclassification over a clinical prediction model, especially for intermediate-risk individuals.
    JACC. Cardiovascular imaging 02/2012; 5(2):131-40. · 14.29 Impact Factor

Publication Stats

13k Citations
2,013.36 Total Impact Points


  • 2006–2014
    • University of Maryland Medical Center
      • • Division of Cardiology
      • • Department of Medicine
      Baltimore, Maryland, United States
    • Brigham and Women's Hospital
      • Department of Medicine
      Boston, MA, United States
  • 2004–2014
    • University of Maryland, Baltimore
      • • Department of Medicine
      • • Division of Cardiology
      Baltimore, Maryland, United States
    • University of Texas Southwestern Medical Center
      • Department of Internal Medicine
      Dallas, TX, United States
    • Johns Hopkins University
      Baltimore, Maryland, United States
    • University of California, Davis
      • School of Medicine
      Davis, CA, United States
  • 2012
    • University of Iowa
      • Department of Internal Medicine
      Iowa City, IA, United States
    • National Institute on Aging
      Baltimore, Maryland, United States
  • 2007–2012
    • Beth Israel Deaconess Medical Center
      • • CardioVascular Institute
      • • Department of Medicine
      Boston, MA, United States
  • 2009–2011
    • Catholic Health Services of Long Island
      New York City, New York, United States
    • Emory University
      • School of Medicine
      Atlanta, GA, United States
  • 2000–2011
    • Wake Forest School of Medicine
      • Section on Cardiology
      Winston-Salem, North Carolina, United States
  • 2005–2010
    • Washington University in St. Louis
      • Division of Cardiovascular Division
      San Luis, Missouri, United States
    • Yeshiva University
      • Ferkauf Graduate School of Psychology
      New York City, NY, United States
  • 2006–2009
    • Duke University Medical Center
      • Duke Clinical Research Institute
      Durham, NC, United States
  • 1999–2009
    • University of Washington Seattle
      • • Division of Cardiology
      • • Department of Medicine
      Seattle, WA, United States
  • 1993–2009
    • Uniformed Services University of the Health Sciences
      • • Department of Medicine
      • • Department of Medical & Clinical Psychology
      Bethesda, MD, United States
  • 2008
    • Weill Cornell Medical College
      New York City, New York, United States
    • University of Groningen
      • Department of Cardiology
      Groningen, Province of Groningen, Netherlands
    • University of Lausanne
      Lausanne, Vaud, Switzerland
  • 2001–2006
    • University of California, Irvine
      • Department of Medicine
      Irvine, CA, United States
    • Saint Luke's Hospital (NY, USA)
      New York City, New York, United States
  • 2000–2006
    • St. Francis Hospital
      Roslyn, New York, United States
  • 2002–2005
    • Saint Francis Hospital
      Tulsa, Oklahoma, United States
  • 1981–2004
    • National Heart, Lung, and Blood Institute
      • • Division of Cardiovascular Sciences (DCVS)
      • • Hematology Branch
      Maryland, United States
  • 2003
    • Singapore Eye Research Institute
      Tumasik, Singapore
  • 1983–2003
    • Georgetown University
      • • Division of Cardiology
      • • Department of Medicine
      Washington, Washington, D.C., United States
  • 2000–2001
    • Washington Hospital Center
      Washington, Washington, D.C., United States
  • 1997–2001
    • University of Massachusetts Medical School
      Worcester, Massachusetts, United States
  • 1987–1997
    • Washington DC VA Medical Center
      Washington, Washington, D.C., United States
  • 1995
    • McGill University
      • Department of Psychiatry
      Montréal, Quebec, Canada
    • Georgia Health Sciences University
      • Medical College of Georgia
      Augusta, GA, United States
  • 1978
    • National Institutes of Health
      Maryland, United States