The publication data currently available has been vetted by Vanderbilt faculty, staff, administrators and trainees. The data itself is retrieved directly from NCBI's PubMed and is automatically updated on a weekly basis to ensure accuracy and completeness.
If you have any questions or comments, please contact us.
Background Few data exist on the long-term risk prediction of elevated left ventricular (LV) mass quantified by MRI for cardiovascular (CV) events in a contemporary, ethnically diverse cohort. Purpose To assess the long-term impact of elevated LV mass on CV events in a prospective cohort study of a multiethnic population in relationship to risk factors and coronary artery calcium (CAC) score. Materials and Methods The Multi-Ethnic Study of Atherosclerosis, or MESA (: NCT00005487), is an ongoing prospective multicenter population-based study in the United States. A total of 6814 participants (age range, 45-84 years) free of clinical CV disease at baseline were enrolled between 2000 and 2002. In 4988 participants (2613 [52.4%] women; mean age, 62 years ± 10.1 [standard deviation]) followed over 15 years for CV events, LV mass was derived from cardiac MRI at baseline enrollment by using semiautomated software at a central core laboratory. Cox proportional hazard models, Kaplan-Meier curves, and scores were applied to assess the impact of LV hypertrophy. Results A total of 290 participants had hard coronary heart disease (CHD) events (207 myocardial infarctions [MIs], 95 CHD deaths), 57 had other CV disease-related deaths, and 215 had heart failure (HF). LV hypertrophy was an independent predictor of hard CHD events (hazard ratio [HR]: 2.7; 95% confidence interval [CI]: 1.9, 3.8), MI (HR: 2.8; 95% CI: 1.8, 4.0), CHD death (HR: 4.3; 95% CI: 2.5, 7.3), other CV death (HR: 7.5; 95% CI: 4.2, 13.5), and HF (HR: 5.4; 95% CI: 3.8, 7.5) ( < .001 for all end points). LV hypertrophy was a stronger predictor than CAC for CHD death, other CV death, and HF ( scores: 5.4 vs 3.4, 6.8 vs 2.4, and 9.7 vs 3.2 for LV hypertrophy vs CAC, respectively). Kaplan-Meier analysis demonstrated an increased risk of CV events in participants with LV hypertrophy, particularly after 5 years. Conclusion Elevated left ventricular mass was strongly associated with hard coronary heart disease events, other cardiovascular death, and heart failure over 15 years of follow-up, independent of traditional risk factors and coronary artery calcium score. © RSNA, 2019 See also the editorial by Hanneman in this issue.
BACKGROUND - Left ventricular (LV) hypertrophy is associated with cerebrovascular disease and cognitive decline. Increased LV mass index is a subclinical imaging marker that precedes overt LV hypertrophy. This study relates LV mass index to white matter microstructure and cognition among older adults with normal cognition and mild cognitive impairment.
METHODS AND RESULTS - Vanderbilt Memory & Aging Project participants free of clinical stroke, dementia, and heart failure (n=318, 73±7 years, 58% male, 39% mild cognitive impairment) underwent brain magnetic resonance imaging, cardiac magnetic resonance, and neuropsychological assessment. Voxelwise analyses related LV mass index (g/m) to diffusion tensor imaging metrics. Models adjusted for age, sex, education, race/ethnicity, Framingham Stroke Risk Profile, cognitive diagnosis, and apolipoprotein E-ε4 status. Secondary analyses included a LV mass index×diagnosis interaction term with follow-up models stratified by diagnosis. With identical covariates, linear regression models related LV mass index to neuropsychological performances. Increased LV mass index related to altered white matter microstructure (<0.05). In models stratified by diagnosis, associations between LV mass index and diffusion tensor imaging were present among mild cognitive impairment participants only (<0.05). LV mass index was related only to worse visuospatial memory performance (β=-0.003, =0.036), an observation that would not withstand correction for multiple testing.
CONCLUSIONS - In the absence of prevalent heart failure and clinical stroke, increased LV mass index corresponds to altered white matter microstructure, particularly among older adults with clinical symptoms of prodromal dementia. Findings highlight the potential link between subclinical LV remodeling and cerebral white matter microstructure vulnerability.
© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.
Prior studies reported associations of APOL1 nephropathy risk variants with subclinical atherosclerosis. However, these findings were limited to older individuals with high comorbidities. To evaluate this in younger individuals, we calculated associations of APOL1 risk variants (high risk [2 risk variants] vs. low risk [0-1 risk variant]) with prevalent, incident, or progressive coronary artery calcification, a carotid intima media thickness over the 90th percentile, and left ventricular hypertrophy in 1315 black participants of the Coronary Artery Risk Development in Young Adults (CARDIA) study. The mean age of this cohort was 44.6 years and their mean estimated glomerular filtration rate was 102.5 ml/min/1.73m. High-risk participants were found to be younger and have a higher prevalence of albuminuria than low-risk participants. In Poisson regression models adjusted for comorbidities and kidney function, the risk of prevalent coronary artery calcification (relative risk [95% confidence interval] 1.12 [0.72,1.71]), the incident coronary artery calcification (1.50 [0.87,2.59]), and the progression of coronary artery calcification (1.40 [0.88,2.23]) did not significantly differ in high vs. low-risk participants. Furthermore, the risk of carotid intima media thickness over the 90th percentile (1.28 [0.78,2.10]) and left ventricular hypertrophy (1.02[0.73,1.43]) did not significantly differ in high vs. low-risk participants in fully-adjusted models. Thus, APOL1 risk variants did not associate with subclinical markers of atherosclerosis or left ventricular hypertrophy in middle-aged black adults with preserved kidney function.
Copyright © 2017 International Society of Nephrology. All rights reserved.
BACKGROUND - Cardiac amyloidosis is an infiltrative cardiomyopathy that is challenging to diagnose. We hypothesized that the novel biomarkers hepatocyte growth factor (HGF), galectin-3 (GAL-3), interleukin-6 (IL-6), and vascular endothelial growth factor (VEGF) would be elevated in cardiac amyloidosis and may be able to discriminate from non-cardiac systemic amyloidosis or other cardiomyopathies with similar clinical or morphologic characteristics.
METHODS - Patients were selected from the Vanderbilt Main Heart Registry according to the following groups: (1) amyloid light-chain (AL) cardiac amyloidosis (n = 26); (2) transthyretin (ATTR) cardiac amyloidosis (n = 7); (3) left ventricular hypertrophy (LVH) (n = 45); (4) systolic heart failure (n = 42); and (5) non-cardiac systemic amyloidosis (n = 7). Biomarkers were measured in stored plasma samples. Biomarkers' discrimination performance in predicting AL cardiac amyloidosis (i.e., Concordance index) was reported. A survival analysis was used to explore the relationship between HGF levels and mortality among AL cardiac amyloidosis patients.
RESULTS - HGF levels were markedly elevated in patients with AL cardiac amyloidosis (median = 622, interquartile range (IQR): 299-1228 pg/mL) compared with the other groups, including those with non-cardiac systemic amyloidosis (median = 134, IQR: 94-163 pg/mL, p < 0.001). HGF was not a specific marker for ATTR amyloidosis. Gal-3 was elevated in all groups with amyloidosis but could not differentiate between those with and without cardiac involvement. There was no difference in IL-6 or VEGF between those with AL cardiac amyloidosis compared to other groups (p = 0.13 and 0.057, respectively).
CONCLUSIONS - HGF may be a specific marker that distinguishes AL cardiac amyloidosis from other cardiomyopathies with similar clinical or morphologic characteristics. Further studies are necessary to determine whether HGF levels predict the likelihood of survival.
IMPORTANCE - Although cardiorespiratory fitness (CRF) is prognostic in older adults, the effect of CRF during early adulthood on long-term cardiovascular structure, function, and prognosis is less clear.
OBJECTIVE - To examine whether CRF in young adults is associated with long-term clinical outcome and subclinical cardiovascular disease (CVD).
DESIGN, SETTING, AND PARTICIPANTS - Prospective study of 4872 US adults aged 18 to 30 years who underwent treadmill exercise testing at a baseline study visit from March 25, 1985, to June 7, 1986, and 2472 individuals who underwent a second treadmill test 7 years later. Median follow-up was 26.9 years, with assessment of obesity, left ventricular mass and strain, coronary artery calcification (CAC), and vital status and incident CVD. Follow-up was complete on August 31, 2011, and data were analyzed from recruitment through the end of follow-up.
MAIN OUTCOMES AND MEASURES - The presence of CAC was assessed by computed tomography at years 15 (2000-2001), 20 (2005-2006), and 25 (2010-2011), and left ventricular mass was assessed at years 5 (1990-1991) and 25 (with global longitudinal strain). Incident CVD and all-cause mortality were adjudicated.
RESULTS - Of the 4872 individuals, 273 (5.6%) died and 193 (4.0%) experienced CVD events during follow-up. After comprehensive adjustment, each additional minute of baseline exercise test duration was associated with a 15% lower hazard of death (hazard ratio [HR], 0.85; 95% CI, 0.80-0.91; P < .001) and a 12% lower hazard of CVD (HR, 0.88; 95% CI, 0.81-0.96; P = .002). Higher levels of baseline CRF were associated with significantly lower left ventricular mass index (β = -0.24; 95% CI, -0.45 to -0.03; P = .02) and significantly better lobal longitudinal strain (β = -0.09; 95% CI, -0.14 to -0.05; P < .001) at year 25. Fitness was not associated with CAC. A 1-minute reduction in fitness by year 7 was associated with 21% and 20% increased hazards of death (HR, 1.21; 95% CI, 1.07-1.37; P = .002) and CVD (HR, 1.20; 95% CI, 1.06-1.37; P = .006), respectively, along with a more impaired strain (β = 0.15; 95% CI, 0.08-0.23; P < .001). No association between change in fitness and CAC was found.
CONCLUSIONS AND RELEVANCE - Higher levels of fitness at baseline and improvement in fitness early in adulthood are favorably associated with lower risks for CVD and mortality. Fitness and changes in fitness are associated with myocardial hypertrophy and dysfunction but not CAC. Regular efforts to ascertain and improve CRF in young adulthood may play a critical role in promoting cardiovascular health and interrupting early CVD pathogenesis.
Aberrant fibroblast growth factor receptor 3 (FGFR3) signaling disrupts chondrocyte proliferation and growth plate size and architecture, leading to various chondrodysplasias or bone overgrowth. These observations suggest that the duration, intensity and cellular context of FGFR signaling during growth plate chondrocyte maturation require tight, regulated control for proper bone elongation. However, the machinery fine-tuning FGFR signaling in chondrocytes is incompletely defined. We report here that neurofibromin, a Ras-GAP encoded by Nf1, has an overlapping expression pattern with FGFR1 and FGFR3 in prehypertrophic chondrocytes, and with FGFR1 in hypertrophic chondrocytes during endochondral ossification. Based on previous evidence that neurofibromin inhibits Ras-ERK signaling in chondrocytes and phenotypic analogies between mice with constitutive FGFR1 activation and Nf1 deficiency in Col2a1-positive chondrocytes, we asked whether neurofibromin is required to control FGFR1-Ras-ERK signaling in maturing chondrocytes in vivo. Genetic Nf1 ablation in Fgfr1-deficient chondrocytes reactivated Ras-ERK1/2 signaling in hypertrophic chondrocytes and reversed the expansion of the hypertrophic zone observed in mice lacking Fgfr1 in Col2a1-positive chondrocytes. Histomorphometric and gene expression analyses suggested that neurofibromin, by inhibiting Rankl expression, attenuates pro-osteoclastogenic FGFR1 signaling in hypertrophic chondrocytes. We also provide evidence suggesting that neurofibromin in prehypertrophic chondrocytes, downstream of FGFRs and via an indirect mechanism, is required for normal extension and organization of proliferative columns. Collectively, this study indicates that FGFR signaling provides an important input into the Ras-Raf-MEK-ERK1/2 signaling axis in chondrocytes, and that this input is differentially regulated during chondrocyte maturation by a complex intracellular machinery, of which neurofibromin is a critical component.
© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: firstname.lastname@example.org.
BACKGROUND - Heart failure (HF) is common and is associated with high mortality. We aimed to determine associations of serum parathyroid hormone (PTH) and 25-hydroxyvitamin D (25[OH]D) with incident HF and left ventricular mass.
METHODS AND RESULTS - Among 6459 participants in the community-based Multi-Ethnic Study of Atherosclerosis, all of whom were free of prevalent clinical cardiovascular disease, we measured serum concentrations of PTH and 25(OH)D at the baseline examination. In longitudinal analyses, we tested associations of PTH and 25(OH)D with incident HF events, adjudicated by a panel of physicians. In cross-sectional analyses of a subset of 4763 participants, we tested associations of PTH and 25(OH)D with left ventricular mass, measured by cardiac magnetic resonance imaging at baseline. Multivariable Cox proportional hazard and linear regression models were adjusted for demographics, physical examination measures, comorbidity, kidney function, and other mineral metabolism markers. Mean age was 62 years and 53% of participants were female. There were 180 incident HF events over a median (interquartile range) follow-up time of 8.46 (7.67 to 8.63) years. Compared with participants with PTH <65 pg/mL, PTH ≥65 pg/mL was associated with a 50% greater risk of incident HF (95% CI: 3% to 210%) and a 5.3 g higher left ventricular mass (95% CI: 2.6, 7.9 g). In contrast, there was no association of 25(OH)D with risk of incident HF or elevated left ventricular mass.
CONCLUSIONS - In a racially/ethnically diverse population without prevalent cardiovascular disease, higher serum PTH concentration was associated with increased left ventricular mass and increased risk of incident HF. Further studies should be pursued to determine whether PTH excess may be a modifiable risk factor for HF.
© 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.
Excess superoxide has been implicated in pulmonary hypertension (PH). We previously found lung overexpression of the antioxidant extracellular superoxide dismutase (EC-SOD) attenuates PH and pulmonary artery (PA) remodeling. Although comprising a small fraction of total SOD activity in most tissues, EC-SOD is abundant in arteries. We hypothesize that the selective loss of vascular EC-SOD promotes hypoxia-induced PH through redox-sensitive signaling pathways. EC-SOD(loxp/loxp) × Tg(cre/SMMHC) mice (SMC EC-SOD KO) received tamoxifen to conditionally deplete smooth muscle cell (SMC)-derived EC-SOD. Mice were exposed to hypobaric hypoxia for 35 days, and PH was assessed by right ventricular systolic pressure measurements and right ventricle hypertrophy. Vascular remodeling was evaluated by morphometric analysis and two-photon microscopy for collagen. We examined cGMP content and soluble guanylate cyclase expression and activity in lung, lung phosphodiesterase 5 (PDE5) expression and activity, and expression of endothelial nitric oxide synthase and GTP cyclohydrolase-1 (GTPCH-1), the rate-limiting enzyme in tetrahydrobiopterin synthesis. Knockout of SMC EC-SOD selectively decreased PA EC-SOD without altering total lung EC-SOD. PH and vascular remodeling induced by chronic hypoxia was augmented in SMC EC-SOD KO. Depletion of SMC EC-SOD did not impact content or activity of lung soluble guanylate cyclase or PDE5, yet it blunted the hypoxia-induced increase in cGMP. Although total eNOS was not altered, active eNOS and GTPCH-1 decreased with hypoxia only in SMC EC-SOD KO. We conclude that the localized loss of PA EC-SOD augments chronic hypoxic PH. In addition to oxidative inactivation of NO, deletion of EC-SOD seems to reduce eNOS activity, further compromising pulmonary vascular function.
Copyright © 2014 the American Physiological Society.
BACKGROUND - Little is known about the clinical significance of coronary artery dilation (CAD) and left ventricular hypertrophy (LVH) in patients with sickle cell disease (SCD).
PROCEDURE - In a retrospective cohort, we studied the prevalence of CAD and LVH in 101 children with SCD in comparison to 93 healthy African-American patients without SCD. Hospital days, number of admissions, and intensive care unit admission after the echocardiogram were assessed as measures of morbidity.
RESULTS - Multivariable analysis of echocardiographic measures of LVH and CAD did not predict subsequent intensive care unit admission, hospital days/year or number of hospital admissions/year during a median follow-up time of 6.1 years. LVH as measured by left ventricular mass index was present in 46% of children with SCD and was inversely related to age (P = 0.0004). Height-indexed dimensions in children with SCD demonstrated that the prevalence of dilation was 49% for the left main coronary artery (LMCA), 29% for the left anterior descending (LAD), and 6% for the right coronary artery (RCA). LMCA dilation was related to relative wall thickness (P = 0.006), inversely to age (P < 0.0006) and weakly to disease severity as determined by hemoglobin (P = 0.03). CAD and LVH were not related to a clinical history of vaso-occlusive pain episode, acute chest syndrome, or cerebrovascular accident.
CONCLUSION - LVH and CAD are common findings in children with SCD; however, they are not associated with need for subsequent hospital or intensive care unit admission.
© 2014 Wiley Periodicals, Inc.
BACKGROUND - After portal vein embolization (PVE), the future liver remnant (FLR) hypertrophies for several weeks. An early marker that predicts a low risk of post-hepatectomy liver failure can reduce the delay to surgery.
STUDY DESIGN - Liver volumes of 153 patients who underwent a major hepatectomy (>3 segments) after PVE for primary or secondary liver malignancy between September 1999 and November 2012 were retrospectively evaluated with computerized volumetry. Pre- and post-PVE FLR volume and functional liver volume were measured. Degree of hypertrophy (DH = post-FLR/post-functional liver volume - pre-FLR/pre-functional liver volume) and growth rate (GR = DH/weeks since PVE) were calculated. Postoperative complications and liver failure were correlated with DH, measured GR, and estimated GR derived from a formula based on body surface area.
RESULTS - Eligible patients underwent 93 right hepatectomies, 51 extended right hepatectomies, 4 left hepatectomies, and 5 extended left hepatectomies. Major complications occurred in 44 patients (28.7%) and liver failure in 6 patients (3.9%). Nonparametric regression showed that post-embolization FLR percent correlated poorly with liver failure. Receiver operating characteristic curves showed that DH and GR were good predictors of liver failure (area under the curve [AUC] = 0.80; p = 0.011 and AUC = 0.79; p = 0.015) and modest predictors of major complications (AUC = 0.66; p = 0.002 and AUC = 0.61; p = 0.032). No patient with GR >2.66% per week had liver failure develop. The predictive value of measured GR was superior to estimated GR for liver failure (AUC = 0.79 vs 0.58; p = 0.046).
CONCLUSIONS - Both DH and GR after PVE are strong predictors of post-hepatectomy liver failure. Growth rate might be a better guide for the optimum timing of liver resection than static volumetric measurements. Measured volumetrics correlated with outcomes better than estimated volumetrics.
Copyright © 2014 American College of Surgeons. Published by Elsevier Inc. All rights reserved.