A Guide for a Cardiovascular Genomics Biorepository: the CATHGEN Experience

Kraus, William E.; Granger, Christopher B.; Sketch, Michael H.; Donahue, Mark; Ginsburg, Geoffrey S.; Hauser, Elizabeth R.; Haynes, Carol; Newby, L. Kristin; Hurdle, Melissa; Dowdy, Z. Elaine; Shah, Svati H.

doi:10.1007/s12265-015-9648-y

Cited by 66 publications

(53 citation statements)

References 40 publications

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“…Details of the biorepository have been previously described. 17,18 Clinical information was obtained from the Duke Databank for Cardiovascular Disease. Available data include symptom histories; clinical characteristics and medical history; angiographic data; and in most subjects, fasting chemistry data within 1 year preceding cardiac catheterization.…”

Section: Methodsmentioning

confidence: 99%

High-density lipoprotein subclass measurements improve mortality risk prediction, discrimination and reclassification in a cardiac catheterization cohort

et al. 2016

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Background and Aims Recent failures of HDL cholesterol (HDL-C)-raising therapies to prevent cardiovascular disease (CVD) events have tempered the interest in the role of HDL-C in clinical risk assessment. Emerging data suggest that the atheroprotective properties of HDL depend on specific HDL particle characteristics not reflected by HDL-C. The purpose of this study was to determine the association of HDL particle concentration (HDL-P) and HDL subclasses with mortality in a high-risk cardiovascular population and to examine the clinical utility of these parameters in mortality risk discrimination and reclassification models. Methods Using nuclear magnetic resonance spectroscopy, we measured HDL-P and HDL subclasses in 3972 individuals enrolled in the CATHGEN coronary catheterization biorepository; tested for association with all-cause mortality in robust clinical models; and examined the utility of HDL subclasses in incremental mortality risk discrimination and reclassification. Results Over an average follow-up of eight years, 29.6% of the individuals died. In a multivariable model adjusted for ten CVD risk factors, HDL-P [HR, 0.71 (0.67-0.76), p= 1.3e-24] had a stronger inverse association with mortality than did HDL-C [HR 0.93 (0.87-0.99), p=0.02]. Larger HDL size conferred greater risk and the sum of medium- and small-size HDL particles (MS-HDL-P) conferred less risk. Furthermore, the strong inverse relation of HDL-P levels with mortality was accounted for entirely by MS-HDL-P; HDL-C was not associated with mortality after adjustment for MS-HDL-P. Addition of MS-HDL-P to the GRACE Risk Score significantly improved risk discrimination and risk reclassification. Conclusion HDL-P and smaller HDL subclasses were independent markers of residual mortality risk and incremental to HDL-C in a high-risk CVD population. These measures should be considered in risk stratification and future development of HDL-targeted therapies in high-risk populations.

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Section: Methodsmentioning

confidence: 99%

High-density lipoprotein subclass measurements improve mortality risk prediction, discrimination and reclassification in a cardiac catheterization cohort

et al. 2016

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“…The cardiac CATHGEN study is approved by the Duke University Institutional Review Board and consists of samples collected from 9,249 sequential consenting adult patients undergoing cardiac catheterization at Duke University Hospital, Durham, NC, USA, between 2001 and 2010 [9]. Consistent with previous studies [2,5,10], we restricted our analysis to 1,641 African-Americans in CATHGEN.…”

Section: Methodsmentioning

confidence: 99%

“…However, an increased CVD risk was not observed in other cohort studies of APOL1 carriers [4,5,8], and no studies so far have examined this association in a secondary cardiovascular prevention population. Thus, to clarify and expand the understanding of APOL1 variants, we assessed the association of APOL1 variants with CKD, coronary artery disease (CAD), and incident CVD events in a secondary cardiovascular prevention population with a high incident CVD event rate, the CATHeterization GENetics (CATHGEN) study [9]. …”

Section: Introductionmentioning

confidence: 99%

Apolipoprotein L1 Genetic Variants Are Associated with Chronic Kidney Disease but Not with Cardiovascular Disease in a Population Referred for Cardiac Catheterization

et al. 2016

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Background: While the association between APOL1 genetic variants and chronic kidney disease (CKD) has been established, their association with cardiovascular disease (CVD) is unclear. This study sought to understand CKD and cardiovascular risk conferred by APOL1 variants in a secondary cardiovascular prevention population. Methods: Two risk variants in APOL1 were genotyped in African-Americans (n = 1,641) enrolled in the CATHGEN biorepository, comprised of patients referred for cardiac catheterization at Duke University Hospital, Durham, NC, USA (2001-2010). Individuals were categorized as noncarriers (n = 722), heterozygote (n = 771), or homozygote carriers (n = 231) of APOL1 risk alleles. Multivariable logistic regression and Cox proportional hazards models adjusted for CVD risk factors were used to assess the association between APOL1 risk variants and prevalent and incident CKD, prevalent coronary artery disease (CAD), incident CVD events, and mortality. Results: The previously identified association between APOL1 variants and prevalent CKD was confirmed (OR: 1.85, 95% CI: 1.33-2.57, p = 0.0002). No statistically significant associations were detected between APOL1 variants and incident CKD or prevalent CAD, incident CVD events or mortality. Age, type 2 diabetes, and ejection fraction at baseline were significant clinical factors that predicted the risk of incident CKD in a subgroup analysis of APOL1 homozygous individuals. Conclusion:APOL1 genetic variants are not associated with CAD or incident CVD events in a cohort of individuals with a high burden of cardiometabolic risk factors. In individuals with homozygous APOL1 status, factors that predicted subsequent CKD included age, presence of type 2 diabetes, and ejection fraction at baseline.

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“…This information should be combined with proteome data—from, e.g., Western blotting, 2D polyacrylamide gel electrophoresis (2D-PAGE), nuclear magnetic resonance (NMR) spectroscopy, and mass spectrometry (MS), or liquid chromatography and tandem mass spectrometry (LC-MS-MS), etc.—to conclude whether particular transcripts are, in fact, being translated and expressed, and in what form and intensity. In view of diverse posttranslational protein modifications, which are key mechanisms to increase proteomic diversity and regulate cellular activities, there is also the question of the biological activity of the protein products and their interaction with endogenous metabolites (endogenous metabolome) and exogenous factors, such as pharmaceuticals (exogenous metabolome) [126, 127]. …”

Section: Piecing Together Genomics Transcriptomics Proteomics Metamentioning

confidence: 99%

Linking Genes to Cardiovascular Diseases: Gene Action and Gene–Environment Interactions

Pasipoularides

2015

J. of Cardiovasc. Trans. Res.

121

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A unique myocardial characteristic is its ability to grow/remodel in order to adapt; this is determined partly by genes and partly by the environment and the milieu intérieur. In the “post-genomic” era, a need is emerging to elucidate the physiologic functions of myocardial genes, as well as potential adaptive and maladaptive modulations induced by environmental/epigenetic factors. Genome sequencing and analysis advances have become exponential lately, with escalation of our knowledge concerning sometimes controversial genetic underpinnings of cardiovascular diseases. Current technologies can identify candidate genes variously involved in diverse normal/abnormal morphomechanical phenotypes, and offer insights into multiple genetic factors implicated in complex cardiovascular syndromes. The expression profiles of thousands of genes are regularly ascertained under diverse conditions. Global analyses of gene expression levels are useful for cataloging genes and correlated phenotypes, and for elucidating the role of genes in maladies. Comparative expression of gene networks coupled to complex disorders can contribute insights as to how “modifier genes” influence the expressed phenotypes. Increasingly, a more comprehensive and detailed systematic understanding of genetic abnormalities underlying, for example, various genetic cardiomyopathies is emerging. Implementing genomic findings in cardiology practice may well lead directly to better diagnosing and therapeutics. There is currently evolving a strong appreciation for the value of studying gene anomalies, and doing so in a non-disjointed, cohesive manner. However, it is challenging for many—practitioners and investigators—to comprehend, interpret, and utilize the clinically increasingly accessible and affordable cardiovascular genomics studies. This survey addresses the need for fundamental understanding in this vital area.

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A Guide for a Cardiovascular Genomics Biorepository: the CATHGEN Experience

Cited by 66 publications

References 40 publications

High-density lipoprotein subclass measurements improve mortality risk prediction, discrimination and reclassification in a cardiac catheterization cohort

High-density lipoprotein subclass measurements improve mortality risk prediction, discrimination and reclassification in a cardiac catheterization cohort

Apolipoprotein L1 Genetic Variants Are Associated with Chronic Kidney Disease but Not with Cardiovascular Disease in a Population Referred for Cardiac Catheterization

Linking Genes to Cardiovascular Diseases: Gene Action and Gene–Environment Interactions

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