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ABSTRACT: BACKGROUND: High-sensitivity cardiac troponin (hs-cTn) assays are now available that can detect measurable troponin in significantly more individuals in the general population than conventional assays. The clinical use of these hs-cTn assays depends on the development of proper reference values. Therefore, our objective was to define hs-cTnI reference values and determinants in the general community, in a healthy reference cohort, and in subsets with diseases.Materials and METHODS: A well-characterized community-based cohort of 2042 study participants underwent clinical assessment and echocardiographic evaluation. Baseline hs-cTnI measurements were obtained in 1843 individuals. A healthy reference cohort (n = 565) without cardiac, renal, or echocardiographic abnormalities was identified.RESULTS: Measurable hs-cTnI was identified in 1716 (93%) of the community-based study cohort and 499 (88%) of the healthy reference cohort. Parameters that significantly contributed to higher hs-cTnI concentrations in the healthy reference cohort included age, male sex, systolic blood pressure, and left ventricular mass. Glomerular filtration rate and body mass index were not independently associated with hs-cTnI in the healthy reference cohort. Individuals with diastolic and systolic dysfunction, hypertension, and coronary artery disease (but not impaired renal function) had significantly higher hs-cTnI values than the healthy reference cohort.CONCLUSIONS: We assessed an hs-cTnI assay with the aid of echocardiographic imaging in a large, well-characterized community-based cohort. hs-cTnI is remarkably sensitive in the general population, and there are important sex and age differences among healthy reference individuals. These results have important implications for defining hs-cTnI reference values and identifying disease.
Clinical Chemistry 04/2013; · 7.91 Impact Factor
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ABSTRACT: OBJECTIVE: To study left ventricular (LV) geometry in patients with rheumatoid arthritis (RA) who have no heart failure (HF) versus subjects without either RA or HF, and to determine the impact of RA on LV remodeling. METHODS: A cross-sectional, community-based study was conducted among adult (≥50 years) RA patients and age- and sex-matched non-RA subjects without a history of HF. All participants underwent a standard 2D/Doppler echocardiography. LV geometry was classified into four categories based on relative wall thickness and sex-specific cut-offs for LV mass index: concentric remodeling, concentric hypertrophy, eccentric hypertrophy, or normal geometry. RESULTS: The study included 200 RA patients and 600 matched non-RA subjects (mean age 65; 74% female in both cohorts). RA patients were significantly more likely to have abnormal LV geometry than non-RA subjects (odds ratio [OR] 1.44; 95% confidence interval [CI] 1.03, 2.00), adjusting for cardiovascular risk factors and comorbidities. Among those with abnormal LV geometry, RA patients had significantly increased odds of concentric LV remodeling (OR 4.73; 95% CI 2.85, 7.83). In linear regression analyses, LV mass index appeared to be lower in RA patients currently using corticosteroids (Beta +/- standard error: -0.082 +/- 0.027; p=0.002), adjusting for cardiovascular risk factors and comorbidities. CONCLUSION: RA was strongly associated with abnormal LV remodeling, particularly, with concentric LV remodeling, among patients without HF. This association was significant beyond adjustment for cardiovascular risk factors and comorbidities. RA disease related factors may promote changes in LV geometry. The biological mechanisms underlying LV remodeling warrant further investigation. © 2013 American College of Rheumatology.
Arthritis & Rheumatism 04/2013; · 7.87 Impact Factor
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Yan Topilsky,
Eugenia Raichlin,
Tal Hasin,
Barry A Boilson,
John A Schirger,
Naveen L Pereira,
Brooks S Edwards,
Alfredo L Clavell, Richard J Rodeheffer,
Robert P Frantz,
Manish J Gandhi,
Simon Maltais,
Soon J Park,
Richard C Daly,
Amir Lerman,
Sudhir S Kushwaha
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ABSTRACT: BACKGROUND: We evaluated whether combined heart and liver transplant (H+LTx) can protect the heart graft from the development of cardiac allograft vasculopathy using coronary three-dimensional (3D) volumetric intravascular ultrasound (IVUS). METHODS: From 2004 to 2009, we identified 24 isolated heart transplant (HTx) and 10 H+LTx recipients in whom two coronary 3D IVUS studies were performed 1 year apart. Baseline 3D IVUS was performed at 0.22 (0.17-1.16) years after transplantation, with follow-up 3D IVUS exams performed after baseline exam (0.96 [0.83-1.08]). RESULTS: Rate of plaque volume and plaque index (plaque volume/vessel volume) progression was attenuated in the H+LTx group (0.3±1.1 vs. 1.5±2.9 mm/mm; P=0.08 and 0.01±0.03 vs. 0.1±0.1; P=0.004, respectively). Rejection burden was much lower in the H+LTx patients. Outcome analysis in 66 consecutive patients (56 HTx and 10 H+LTx) was performed irrespective of performance of second coronary IVUS. H+LTx was associated with reduced rate of cardiac events (P=0.04), which remained significant when adjusted for the difference in the primary etiology for heart disease (P=0.05). CONCLUSIONS: Our preliminary serial 3D coronary IVUS data show that H+LTx attenuates cardiac allograft vasculopathy by decreasing the rate of plaque volume and plaque index progression and improves coronary-related outcomes. Because of the small numbers and the differences in etiology of heart disease, our data should be interpreted cautiously, and larger clinical trials would be required to recommend H+LTx for improved coronary remodeling.
Transplantation 01/2013; · 4.00 Impact Factor
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Yan Topilsky,
Manish J Gandhi,
Tal Hasin,
Laurie L Voit,
Eugenia Raichlin,
Barry A Boilson,
John A Schirger,
Brooks S Edwards,
Alfredo L Clavell, Richard J Rodeheffer,
Robert P Frantz,
Sudhir S Kushwaha,
Amir Lerman,
Naveen L Pereira
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ABSTRACT: Although a link between donor-specific antibodies against human leukocyte antigens type II (DSA II+) and transplant glomerulopathy has been clearly established, its role in cardiac allograft vasculopathy (CAV) is unclear.
Donor-specific antibodies were evaluated using solid-phase single-antigen bead assay before transplantation in 51 heart transplant recipients. Coronary angiography and three-dimensional intravascular ultrasound were performed at baseline and approximately 1 year after the baseline examination.
There were 4 (7.8 %), 11 (21.5%), and 2 (3.9%) patients who had DSA against donor class I (DSA I+), DSA II+, or both, respectively. All patients had negative complement-dependent cytotoxic crossmatch. There was accelerated progression of CAV in the DSA II+ group demonstrated by accelerated progression in plaque index (plaque volume/vessel volume) compared to patients with no DSA II+ antibodies (13.8% [12%] vs. -7.9% [37%], P=0.01). The development of any angiographic CAV was also more common in DSA II+ patients as compared to the DSA- patients at 4 years (100% [0%] vs. 64.2% [10%], P=0.05). All other traditional risk factors for CAV or immunosuppression were similar between the groups (P>0.2 for all).
This is the first preliminary study demonstrating that heart transplant recipients with preformed class II DSA may be at an increased risk for accelerated CAV as detected by consecutive volumetric three-dimensional intravascular ultrasound.
Transplantation 01/2013; 95(2):389-96. · 4.00 Impact Factor
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Tal Hasin,
Yariv Marmor,
Walter Kremers,
Yan Topilsky,
Cathy J Severson,
John A Schirger,
Barry A Boilson,
Alfredo L Clavell, Richard J Rodeheffer,
Robert P Frantz,
Brooks S Edwards,
Naveen L Pereira,
John M Stulak,
Lyle Joyce,
Richard Daly,
Soon J Park,
Sudhir S Kushwaha
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ABSTRACT: OBJECTIVES: The purpose of this study was to determine the occurrence and causes of readmissions after implantation of axial flow left ventricular assist device (LVAD). BACKGROUND: Based on the REMATCH (Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure) study experience, readmissions after LVAD implantation are thought to be frequent. METHODS: We retrospectively analyzed admissions to our facility in a cohort of 115 patients implanted between January 2008 and July 2011 with the HeartMate II axial flow LVAD, of whom 42 were bridged to transplant. To account for repeated events, Andersen-Gill models were used to determine possible predictors. RESULTS: The patients were followed for 1.4 ± 0.9 years. There were 224 readmissions in 83 patients. The overall readmission rate was 1.64 ± 1.97 per patient-year of follow-up. The readmission rate for the first 6 months was 2.0 ± 2.3 and decreased to 1.2 ± 2.1 during subsequent follow-up. Leading causes were bleeding (66 readmissions in 34 patients), mostly gastrointestinal bleed (51 in 27 patients), cardiac (51 in 36 patients, most for HF or arrhythmia), infections (32 in 25 patients) of which 6 were pump related, and thrombosis (20 in 15 patients) including 13 readmissions due to hemolysis. Preoperative variables associated with (fewer) readmissions in a multivariate model include residence within our hospital-extended referral zone of Minnesota and the neighboring states (hazard ratio: 0.66; 95% confidence interval: 0.48 to 0.91; p = 0.011), hemoglobin (hazard ratio: 0.91, 95% confidence interval: 0.84 to 0.99; p = 0.027) and N-terminal pro-B-type natriuretic peptide (hazard ratio: 0.98; 95% confidence interval: 0.96 to 1.0 per 1,000-unit increase, p = 0.022). C-statistic for the model: 0.63. CONCLUSIONS: Readmission rates after axial flow LVAD implantation decrease during the first 6 months and then stabilize. The leading causes are bleeding, cardiac (heart failure and arrhythmia), infections, and thrombosis.
Journal of the American College of Cardiology 11/2012; · 14.16 Impact Factor
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ABSTRACT: BACKGROUND: -Patients with heart failure and preserved ejection fraction (HFpEF) display increased adiposity and multiple comorbidities, factors that in themselves may influence cardiovascular (CV) structure and function. This has sparked debate as to whether HFpEF represents a distinct disease or an amalgamation of comorbidities. We hypothesized that fundamental CV structural and functional alterations are characteristic of HFpEF, even after accounting for body size and comorbidities. METHODS AND RESULTS: -Comorbidity adjusted CV structural and functional parameters scaled to independently generated and age appropriate allometric powers were compared in community-based cohorts of HFpEF patients (n=386) and age/gender-matched healthy (CON, n=193) and hypertensive (HTN, n=386) controls. Within HFpEF patients, body size and concomitant comorbidity adjusted CV structural and functional parameters and survival were compared in those with and without individual comorbidities. Among HFpEF patients, comorbidities (obesity, anemia, diabetes and renal dysfunction) were each associated with unique clinical, structural, functional and prognostic profiles. However, after accounting for age, gender, body size and comorbidities, greater concentric hypertrophy, atrial enlargement and systolic, diastolic and vascular dysfunction were consistently observed in HFpEF compared to CON and HTN. CONCLUSIONS: -Comorbidities influence ventricular-vascular properties and outcomes in HFpEF, yet fundamental disease-specific changes in cardiovascular structure and function underlie this disorder. These data support the search for mechanistically-targeted therapies in this disease.
Circulation Heart Failure 10/2012; · 6.29 Impact Factor
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Tal Hasin,
Yan Topilsky,
Walter K Kremers,
Barry A Boilson,
John A Schirger,
Brooks S Edwards,
Alfredo L Clavell, Richard J Rodeheffer,
Robert P Frantz,
Lyle Joyce,
Richard Daly,
John M Stulak,
Sudhir S Kushwaha,
Soon J Park,
Naveen L Pereira
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ABSTRACT: The goal of this study was to describe the predictors and significance of poor exercise tolerance after left ventricular assist device (LVAD) implantation. Despite LVAD therapy, some patients continue to exhibit exercise intolerance. The predictors and outcomes of these patients are unknown. A retrospective review of 65 LVAD recipients who performed 6-minute walk tests was conducted. Patients walking <300 m were considered to have poor exercise tolerance. Twenty patients exhibited poor exercise tolerance (221 ± 45 m), compared to 45 patients with better exercise tolerance (406 ± 76 m). Postoperatively, poor performers were not easily identified by functional symptoms alone, because 42% of these patients reported New York Heart Association functional class I or II symptoms. Preoperative New York Heart Association class, inotrope therapy, and intra-aortic balloon pump use were similar between the 2 groups. Multivariate analysis using all adequately powered (n >50) univariate predictors identified diabetes mellitus (odds ratio 10.493, p = 0.003) and elevated 1-month right atrial pressure (odds ratio 2.985 for every 5 mm Hg, p = 0.003) as significant predictors of poor performance (<300 m; area under the curve 0.85). The poorly performing group had increased mortality (p = 0.011), with 21% increased risk for overall mortality for every 10 m short of 300 m (fitted Cox model: hazard ratio 1.211, p = 0.0001). The distance walked in meters in a postoperative 6-minute walk test was the strongest predictor of late post-LVAD mortality (p = 0.0002). In conclusion, despite similar severity of heart failure preoperatively, some LVAD recipients may have persistent exercise intolerance postoperatively as assessed by the 6-minute walk test that is independently associated with subsequent reduced survival.
The American journal of cardiology 07/2012; 110(9):1322-8. · 3.58 Impact Factor
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ABSTRACT: The pathophysiology of heart failure with preserved ejection fraction (HFpEF) is complex but increased left ventricular (LV) diastolic stiffness plays a key role. A load-independent, non-invasive, direct measure of diastolic stiffness is lacking. The diastolic wall strain (DWS) index is based on the linear elastic theory, which predicts that impaired diastolic wall thinning reflects resistance to deformation in diastole and thus, increased diastolic myocardial stiffness. The objectives of this community-based study were to determine the distribution of this novel index in consecutive HFpEF patients and healthy controls, define the relationship between DWS and cardiac structure and function and determine whether increased diastolic stiffness as assessed by DWS is predictive of the outcome in HFpEF.
Consecutive HFpEF patients (n = 327, EF ≥ 50%) and controls (n = 528) from the same community were studied. Diastolic wall strain was lower in HFpEF (0.33 ± 0.08) than in controls (0.40 ± 0.07, P < 0.001). Within HFpEF, those with DWS ≤ median (0.33) had higher LV mass index, relative wall thickness, E/e', Doppler-estimated LV end-diastolic pressure to LV end-diastolic volume ratio, left atrial volume index, and brain natriuretic peptide (BNP) levels than those with DWS > median. Heart failure with preserved ejection fraction patients with DWS ≤ median had higher rate of death or HF hospitalization than those with DWS > median (P = 0.003) even after the adjustment for age, gender, log BNP, LV geometry, or log E/e' (P < 0.01).
These data suggest that DWS, a simple index, is useful in assessing diastolic stiffness and that more advanced diastolic stiffness is associated with worse outcomes in HFpEF.
European Heart Journal 05/2012; 33(14):1742-9. · 10.48 Impact Factor
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ABSTRACT: ATP-sensitive K+ (KATP) channel mutations have been identified in individuals with dilated cardiomyopathy and overt heart failure. Here, a common
E23K functional polymorphism in the Kir6.2 channel pore versus cardiac phenotype was studied in a cross-sectional community-based
cohort (n=2,031). The KK genotype was associated with greater left ventricular size among subjects with increased stress load due
to hypertension. These findings implicate Kir6.2 K23 as a risk factor for adverse subclinical myocardial remodeling, and underscore
the significance of cardiac KATP channels within the population.
Human Genetics 04/2012; 123(6):665-667. · 5.07 Impact Factor
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Tal Hasin,
Yan Topilsky,
John A Schirger,
Zhuo Li,
Yanjun Zhao,
Barry A Boilson,
Alfredo L Clavell, Richard J Rodeheffer,
Robert P Frantz,
Brooks S Edwards,
Naveen L Pereira,
Lyle Joyce,
Richard Daly,
Soon J Park,
Sudhir S Kushwaha
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ABSTRACT: The aim of this study was to determine renal outcomes after left ventricular assist device (LVAD) implantation.
Renal dysfunction before LVAD placement is frequent, and it is unclear whether it is due to primary renal disease or to poor perfusion.
A retrospective single-center analysis was conducted in 83 consecutive patients implanted with HeartMate II continuous-flow LVADs (Thoratec Corp., Pleasanton, California). Calculated glomerular filtration rate (GFR) was assessed on admission and 1, 3, and 6 months after implantation. To define predictors for improvement in GFR, clinical variables were examined in patients with decreased renal function (GFR <60 ml/min/1.73 m(2)) before LVAD, surviving and dialysis-free at 1 month (n = 44).
GFR significantly increased from admission (53.2 ± 21.4 ml/min/1.73 m(2)) to 1 month after LVAD implantation (87.4 ± 27.9 ml/min/1.73 m(2)) (p < 0.0001). Subsequently, at 3 and 6 months, GFR remained significantly (p < 0.0001) above pre-LVAD values. Of the 51 patients with GFRs <60 ml/min/1.73 m(2) before LVAD surviving at 1 month, 34 (67%) improved to GFRs >60 ml/min/1.73 m(2). Univariate pre-operative predictors for improvement in renal function at 1 month included younger age (p = 0.049), GFR improvement with optimal medical therapy (p < 0.001), intra-aortic balloon pump use (p = 0.004), kidney length above 10 cm (p = 0.023), no treatment with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (p = 0.029), higher bilirubin (p = 0.002), higher Lietz-Miller score (p = 0.019), and atrial fibrillation (p = 0.007). Multivariate analysis indicated pre-operative improved GFR (slope = 0.5 U per unit improved; 95% confidence interval: 0.2 to 0.8; p = 0.003), atrial fibrillation (slope = 27; 95% confidence interval: 8 to 46; p = 0.006), and intra-aortic balloon pump use (slope = 14; 95% confidence interval: 2 to 26; p = 0.02) as independent predictors.
In most patients with end-stage heart failure considered for LVAD implantation, renal dysfunction is reversible and likely related to poor renal perfusion.
Journal of the American College of Cardiology 01/2012; 59(1):26-36. · 14.16 Impact Factor
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Yan Topilsky,
Tal Hasin,
Eugenia Raichlin,
Barry A Boilson,
John A Schirger,
Naveen L Pereira,
Brooks S Edwards,
Alfredo L Clavell, Richard J Rodeheffer,
Robert P Frantz,
Simon Maltais,
Soon J Park,
Richard C Daly,
Amir Lerman,
Sudhir S Kushwaha
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ABSTRACT: We retrospectively analyzed the potential of sirolimus as a primary immunosuppressant in the long-term attenuation of cardiac allograft vasculopathy progression and the effects on cardiac-related morbidity and mortality.
Forty-five cardiac transplant recipients were converted to sirolimus 1.2 years (0.2, 4.0) after transplantation with complete calcineurin inhibitor withdrawal. Fifty-eight control subjects 2.0 years (0.2, 6.5 years) from transplantation were maintained on calcineurin inhibitors. Age, sex, ejection fraction, and time from transplantation to baseline intravascular ultrasound study were not different (P>0.2 for all) between the groups; neither were secondary immunosuppressants and use of steroids. Three-dimensional intravascular ultrasound studies were performed at baseline and 3.1 years (1.3, 4.6 years) later. Plaque index progression (plaque volume/vessel volume) was attenuated in the sirolimus group (0.7±10.5% versus 9.3±10.8%; P=0.0003) owing to reduced plaque volume in patients converted to sirolimus early (<2 years) after transplantation (P=0.05) and improved positive vascular remodeling (P=0.01) in patients analyzed late (>2 years) after transplantation. Outcome analysis in 160 consecutive patients maintained on 1 therapy was performed regardless of performance of intravascular ultrasound examinations. Five-year survival was improved with sirolimus (97.4±1.8% versus 81.8±4.9%; P=0.006), as was freedom from cardiac-related events (93.6±3.2% versus 76.9±5.5%; P=0.002).
Substituting calcineurin inhibitor with sirolimus as primary immunosuppressant attenuates long-term cardiac allograft vasculopathy progression and may improve long-term allograft survival owing to favorable coronary remodeling. Because of the lack of randomization and retrospective nature of our analysis, the differences in outcome should be interpreted cautiously, and prospective clinical trials are required.
Circulation 12/2011; 125(5):708-20. · 14.74 Impact Factor
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ABSTRACT: To determine the predictive value of atrial natriuretic peptide (ANP), N-terminal pro-ANP (NT-proANP), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) for mortality and cardiovascular events in the general population in the absence of overt heart failure (HF).
We identified a community-based cohort of 2042 individuals. Those with stage C or D HF (n=45) and renal insufficiency (n=6) were excluded from the current study. Of the remaining individuals, 1769 (89%) underwent echocardiography and measurement of plasma ANP, NT-proANP, and NT-proBNP. Participants were followed up from January 1, 1997, to May 1, 2009, for mortality, HF, myocardial infarction (MI), and cerebrovascular accident; median follow-up was 9 years.
After adjustment for conventional clinical risk factors, NT-proANP had significant predictive value for mortality but not for HF, MI, or cerebrovascular accident, whereas ANP lacked any predictive value. The predictive value of NT-proANP for mortality was attenuated after adjustment for structural and functional cardiac abnormalities. In contrast, NT-proBNP had predictive value for mortality, HF, and MI after adjustment for conventional risk factors and retained significance for mortality and HF after adjustment for structural and functional cardiac abnormalities.
Our results suggest that NT-proBNP is a more robust cardiac biomarker compared with ANP or NT-proANP and is independently predictive of mortality and HF in the general population free of overt HF.
Mayo Clinic Proceedings 12/2011; 86(12):1154-60. · 5.70 Impact Factor
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Richard J Rodeheffer
Circulation 10/2011; 124(17):1803-5. · 14.74 Impact Factor
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ABSTRACT: Heart failure incidence increases with advancing age, and approximately half of patients with heart failure have preserved left ventricular ejection fraction. Although diastolic dysfunction plays a role in heart failure with preserved ejection fraction, little is known about age-dependent longitudinal changes in diastolic function in community populations.
To measure changes in diastolic function over time and to determine the relationship between diastolic dysfunction and the risk of subsequent heart failure.
Population-based cohort of participants enrolled in the Olmsted County Heart Function Study. Randomly selected participants 45 years or older (N = 2042) underwent clinical evaluation, medical record abstraction, and echocardiography (examination 1 [1997-2000]). Diastolic left ventricular function was graded as normal, mild, moderate, or severe by validated Doppler techniques. After 4 years, participants were invited to return for examination 2 (2001-2004). The cohort of participants returning for examination 2 (n = 1402 of 1960 surviving [72%]) then underwent follow-up for ascertainment of new-onset heart failure (2004-2010).
Change in diastolic function grade and incident heart failure.
During the 4 (SD, 0.3) years between examinations 1 and 2, diastolic dysfunction prevalence increased from 23.8% (95% confidence interval [CI], 21.2%-26.4%) to 39.2% (95% CI, 36.3%-42.2%) (P < .001). Diastolic function grade worsened in 23.4% (95% CI, 20.9%-26.0%) of participants, was unchanged in 67.8% (95% CI, 64.8%-70.6%), and improved in 8.8% (95% CI, 7.1%-10.5%). Worsened diastolic dysfunction was associated with age 65 years or older (odds ratio, 2.85 [95% CI, 1.77-4.72]). During 6.3 (SD, 2.3) years of additional follow-up, heart failure occurred in 2.6% (95% CI, 1.4%-3.8%), 7.8% (95% CI, 5.8%-13.0%), and 12.2% (95% CI, 8.5%-18.4%) of persons whose diastolic function normalized or remained normal, remained or progressed to mild dysfunction, or remained or progressed to moderate or severe dysfunction, respectively (P < .001). Diastolic dysfunction was associated with incident heart failure after adjustment for age, hypertension, diabetes, and coronary artery disease (hazard ratio, 1.81 [95% CI, 1.01-3.48]).
In a population-based cohort undergoing 4 years of follow-up, prevalence of diastolic dysfunction increased. Diastolic dysfunction was associated with development of heart failure during 6 years of subsequent follow-up.
JAMA The Journal of the American Medical Association 08/2011; 306(8):856-63. · 30.03 Impact Factor
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Valentina Cannone,
Guido Boerrigter,
Alessandro Cataliotti,
Lisa C Costello-Boerrigter,
Timothy M Olson,
Paul M McKie,
Denise M Heublein,
Brian D Lahr,
Kent R Bailey,
Maurizio Averna,
Margaret M Redfield, Richard J Rodeheffer,
John C Burnett
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ABSTRACT: We sought to define the cardiometabolic phenotype associated with rs5068, a genetic variant of the atrial natriuretic peptide (ANP) gene.
The ANP and B-type natriuretic peptide play an important role in cardiorenal homeostasis but also exert metabolic actions.
We genotyped 1,608 randomly selected residents from Olmsted County, Minnesota. Subjects were well-characterized.
Genotype frequencies were: AA 89.9%, AG 9.7%, and GG 0.4%; all subsequent analyses were AA versus AG+GG. The G allele was associated with increased plasma levels of N-terminal pro-atrial natriuretic peptide (p = 0.002), after adjustment for age and sex. The minor allele was also associated with lower body mass index (BMI) (p = 0.006), prevalence of obesity (p = 0.002), waist circumference (p = 0.021), lower levels of C-reactive protein (p = 0.027), and higher values of high-density lipoprotein cholesterol (p = 0.019). The AG+GG group had a lower systolic blood pressure (p = 0.011) and lower prevalence of myocardial infarction (p = 0.042). The minor allele was associated with a lower prevalence of metabolic syndrome (p = 0.025). The associations between the G allele and high-density lipoprotein cholesterol, C-reactive protein values, myocardial infarction, and metabolic syndrome were not significant, after adjusting for BMI; the associations with systolic blood pressure, BMI, obesity, and waist circumference remained significant even after adjusting for N-terminal pro-atrial natriuretic peptide.
In a random sample of the general U.S. population, the minor allele of rs5068 is associated with a favorable cardiometabolic profile. These findings suggest that rs5068 or genetic loci in linkage disequilibrium might affect susceptibility for cardiometabolic diseases and support the possible protective role of natriuretic peptides by their favorable effects on metabolic function. Replication studies are needed to confirm our findings.
Journal of the American College of Cardiology 08/2011; 58(6):629-36. · 14.16 Impact Factor
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Eugenia Raichlin,
Malik A Al-Omari,
Courtney L Hayes,
Brooks S Edwards,
Robert P Frantz,
Barry A Boilson,
Alfredo L Clavell, Richard J Rodeheffer,
John A Schirger,
Sudhir S Kushwaha,
Thomas G Allison,
Naveen L Pereira
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ABSTRACT: Exercise performance, an important aspect of quality of life, remains limited after heart transplantation (HTx). This study examines the effect of cardiac allograft remodeling on functional capacity after HTx.
The total cohort of 117 HTx recipients, based on echocardiographic determination of left ventricle mass and relative wall thickness at 1 year after HTx, was divided into 3 groups: (1) NG, normal geometry; (2) CR, concentric remodeling; and (3) CH, concentric hypertrophy. Cardiopulmonary exercise testing was performed 5.03 ± 3.08 years after HTx in all patients. Patients with acute rejection or significant graft vasculopathy were excluded.
At 1 year post-HTx, 30% of patients had CH, 55% had CR and 15% had NG. Exercise tolerance, measured by maximum achieved metabolic equivalents (4.62 ± 1.44 vs 5.52 ± 0.96 kcal/kg/h), normalized peak Vo(2) (52 ± 14% vs 63 ± 12%) and Ve/Vco(2) (41 ± 17 vs 34 ± 6), was impaired in the CH group compared with the NG group. A peak Vo(2) ≤14 ml/kg/min was found in 6%, 22% and 48% of patients in the NG, CR and CH groups, respectively (p = 0.01). The CH pattern was associated with a 7.4-fold increase in relative risk for a peak Vo(2) ≤14 ml/kg/min compared with NG patients (95% confidence interval 1.1 to 51.9, p = 0.001). After multivariate analysis, a 1-year CH pattern was independently associated with a reduced normalized peak Vo(2) (p = 0.018) and an elevated Ve/Vco(2) (p = 0.035).
The presence of CH at 1 year after HTx is independently associated with decreased normalized peak Vo(2) and increased ventilatory response in stable heart transplant recipients. The identification of CH, a potentially reversible mechanism of impairment in exercise capacity after HTx, may have major clinical implications.
The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation 05/2011; 30(10):1153-60. · 3.54 Impact Factor
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ABSTRACT: To assess in a US general adult population the effect of the functional single-nucleotide polymorphism rs198389 in the promoter region of the gene of brain-type natriuretic peptide (BNP) on 3 commonly used BNP assays, clinical phenotype, disease prevalence, overall survival, and diagnostic test characteristics of BNP as a biomarker.
We genotyped for rs198389 in a random sample of the general population (aged ≥ 45 years; n = 1970; enrolled between June 1, 1997, and September 30, 2000) from Olmsted County, Minnesota. Patients were characterized biochemically, clinically, echocardiographically, and regarding BNP molecular forms (2 assays for BNP and 1 assay for amino-terminal proBNP). Median follow-up was 9 years.
Genotype frequencies were in Hardy-Weinberg equilibrium (P = .98): TT genotype, n = 645 (32.7%); TC genotype, n = 983 (49.9%); and CC genotype, n = 342 (17.4%). The C allele independently predicted higher BNP forms (P<.001 for all assays). Genotypes did not differ with regard to clinical and echocardiographic phenotype or overall survival. When previously reported genotype-unadjusted cut points for the detection of left ventricular ejection fraction less than or equal to 40% (n = 37 [1.9%]) and less than or equal to 50% (n = 116 [6.0%]) were used, sensitivity generally increased with the number of C alleles, whereas specificity decreased, both on average by more than 10% for the TT vs CC genotype.
The C allele of rs198389 is common in the general US population and is associated with higher concentrations of BNP molecular forms but not with cardiovascular phenotype or survival. The C allele confounds the test characteristics of commonly used assays.
Mayo Clinic Proceedings 03/2011; 86(3):210-8. · 5.70 Impact Factor
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ABSTRACT: Patients with rheumatoid arthritis (RA) are at an increased risk for heart failure and left ventricular diastolic dysfunction (LVDD). B-type natriuretic peptide (BNP) may be useful to screen for LVDD in the general population. We compared the effectiveness of BNP as a screening tool for LVDD in RA and non-RA subjects without cardiovascular disease (CVD).
Study subjects were recruited from population-based samples with and without RA, excluding subjects with CVD. LVDD was assessed by 2-dimensional and Doppler echocardiography and categorized as none, mild, moderate/severe, or indeterminate. Linear regression and proportional odds models evaluated the association between LVDD and BNP, adjusting for age, sex, and body mass index.
Among 231 RA and 1,730 non-RA subjects without CVD, BNP was significantly higher in subjects with moderate/severe LVDD compared to those with no or mild LVDD (P = 0.02 for RA and P < 0.001 for non-RA subjects). More RA subjects had elevated BNP than non-RA subjects (16% versus 9%; P < 0.001). Positive predictive value (25% in RA and 18% in non-RA subjects) and sensitivity (40% in RA and 26% in non-RA subjects) were similarly low in both cohorts, but specificity was significantly lower in RA than in non-RA subjects (89% versus 94%; P = 0.02).
While RA subjects were more likely to have elevated BNP, few RA patients with elevated BNP actually have LVDD. Also, normal BNP levels are less likely to rule out LVDD in RA than in non-RA subjects. Therefore, BNP may be less effective for screening in RA subjects compared to the general population.
Arthritis care & research. 01/2011; 63(5):729-34.
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ABSTRACT: to examine whether patients with rheumatoid arthritis (RA) with no overt cardiovascular disease (CVD) have a higher prevalence of metabolic syndrome (MetS) than subjects without RA or CVD. We also examined whether RA disease characteristics are associated with the presence of MetS in RA patients without CVD.
subjects from a population-based cohort of patients who fulfilled 1987 American College of Rheumatology criteria for RA between January 1, 1980, and December 31, 2007, were compared to non-RA subjects from the same population. All subjects with any history of CVD were excluded. Waist circumference, body mass index (BMI), and blood pressure were measured during the study visit. Data on CVD, lipids, and glucose measures were ascertained from medical records. MetS was defined using NCEP/ATP III criteria. Differences between the 2 cohorts were examined using logistic regression models adjusted for age and sex.
the study included 232 RA subjects without CVD and 1241 non-RA subjects without CVD. RA patients were significantly more likely to have increased waist circumference and elevated blood pressure than non-RA subjects, even though BMI was similar in both groups. Significantly more RA patients were classified as having MetS. In RA patients, MetS was associated with Health Assessment Questionnaire Disability Index, large-joint swelling, and uric acid levels, but not with C-reactive protein or RA therapies.
among subjects with no history of CVD, patients with RA are more likely to have MetS than non-RA subjects. MetS in patients with RA was associated with some measures of disease activity.
The Journal of Rheumatology 10/2010; 38(1):29-35. · 3.69 Impact Factor
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ABSTRACT: Our objective was to determine the prognostic value of plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) for death and cardiovascular events among subjects without risk factors for heart failure (HF), which we term healthy normal.
Previous studies report that plasma NT-proBNP has prognostic value for cardiovascular events in the general population even in the absence of HF. It is unclear if NT-proBNP retains predictive value in healthy normal subjects.
We identified a community-based cohort of 2,042 subjects in Olmsted County, Minnesota. Subjects with symptomatic (stage C/D) HF were excluded. The remaining 1,991 subjects underwent echocardiography and NT-proBNP measurement. We further defined healthy normal (n = 703) and stage A/B HF (n = 1,288) subgroups. Healthy normal was defined as the absence of traditional clinical cardiovascular risk factors and echocardiographic structural cardiac abnormalities. Subjects were followed for death, HF, cerebrovascular accident, and myocardial infarction with median follow-up of 9.1, 8.7, 8.8, and 8.9 years, respectively.
NT-proBNP was not predictive of death or cardiovascular events in the healthy normal subgroup. Similar to previous reports, in stage A/B HF, plasma NT-proBNP values greater than age-/sex-specific 80th percentiles were associated with increased risk of death, HF, cerebrovascular accident, and myocardial infarction (p < 0.001 for all) even after adjustment for clinical risk factors and structural cardiac abnormalities.
These findings do not support the use of NT-proBNP as a cardiovascular biomarker in healthy normal subjects and have important implications for NT-proBNP-based strategies for early detection and primary prevention of cardiovascular disease.
Journal of the American College of Cardiology 05/2010; 55(19):2140-7. · 14.16 Impact Factor
