Multiomic Profiling in Black and White Populations Reveals Novel Candidate Pathways in Left Ventricular Hypertrophy and Incident Heart Failure Specific to Black Adults

Katz, Daniel H.; Tahir, Usman A.; Ngo, Debby; Benson, Mark D.; Gao, Yan; Shi, Xu; Nayor, Matthew; Keyes, Michelle J.; Larson, Martin G.; Hall, Michael E.; Correa, Adolfo; Sinha, Sumita; Shen, Dongxiao; Herzig, Matthew; Yang, Qiong; Robbins, Jeremy; Chen, Zsu-Zsu; Cruz, Daniel; Peterson, Bennet; Vasan, Ramachandran S.; Wang, Thomas J.; Wilson, James G.; Gerszten, Robert E.

doi:10.1161/circgen.120.003191

Cited by 7 publications

(5 citation statements)

References 59 publications

(67 reference statements)

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“…We identified several established markers of HF risk (NT-proBNP, GDF-15) 19 , 20 , confirmed previously described associations of other proteins with incident HF (e.g. SPON1 8 – 10 , THBS2 5 , 7 , GHR 6 , IFGBP2 5 , 6 , C9 7 , osteoprotogerin 8 , 10 , MMP12 8 – 10 ), and identified several proteins not previously associated with incident HF (e.g. SVEP1, FSTL3, APOF, ANGPTL3, IGFBP7, CCL15, and ITIH3 among others).…”

Section: Discussionsupporting

confidence: 87%

Large scale plasma proteomics identifies novel proteins and protein networks associated with heart failure development

Shah,

Myhre,

Arthur

et al. 2024

Nat Commun

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Heart failure (HF) causes substantial morbidity and mortality but its pathobiology is incompletely understood. The proteome is a promising intermediate phenotype for discovery of novel mechanisms. We measured 4877 plasma proteins in 13,900 HF-free individuals across three analysis sets with diverse age, geography, and HF ascertainment to identify circulating proteins and protein networks associated with HF development. Parallel analyses in Atherosclerosis Risk in Communities study participants in mid-life and late-life and in Trøndelag Health Study participants identified 37 proteins consistently associated with incident HF independent of traditional risk factors. Mendelian randomization supported causal effects of 10 on HF, HF risk factors, or left ventricular size and function, including matricellular (e.g. SPON1, MFAP4), senescence-associated (FSTL3, IGFBP7), and inflammatory (SVEP1, CCL15, ITIH3) proteins. Protein co-regulation network analyses identified 5 modules associated with HF risk, two of which were influenced by genetic variants that implicated trans hotspots within the VTN and CFH genes.

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Section: Discussionsupporting

confidence: 87%

Large scale plasma proteomics identifies novel proteins and protein networks associated with heart failure development

Shah,

Myhre,

Arthur

et al. 2024

Nat Commun

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“…Previous work has linked fractalkine, an inflammatory cytokine, to incident heart failure, specifically in Black individuals. 63…”

Section: Novel Genetic Determinants Of Plasma Proteins Related To Thr...mentioning

confidence: 99%

Whole Genome Sequence Analysis of the Plasma Proteome in Black Adults Provides Novel Insights Into Cardiovascular Disease

et al. 2022

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Background: Plasma proteins are critical mediators of cardiovascular processes and are the targets of many drugs. Previous efforts to characterize the genetic architecture of the plasma proteome have been limited by a focus on individuals of European descent and leveraged genotyping arrays and imputation. Here we describe whole genome sequence analysis of the plasma proteome in individuals with greater African ancestry, increasing our power to identify novel genetic determinants. Methods: Proteomic profiling of 1,301 proteins was performed in 1852 Black adults from the Jackson Heart Study using aptamer-based proteomics (SomaScan ® ). Whole genome sequencing association analysis was ascertained for all variants with minor allele count ≥ 5. Results were validated using an alternative, antibody-based, proteomic platform (Olink ® ) as well as replicated in the Multi-Ethnic Study of Atherosclerosis and the HERITAGE Family Study. Results: We identify 569 genetic associations between 479 proteins and 438 unique genetic regions at a Bonferroni-adjusted significance level of 3.8 × 10 −11 . These associations include 114 novel locus-protein relationships and an additional 217 novel sentinel variant-protein relationships. Novel cardiovascular findings include new protein associations at the APOE gene locus including ZAP70 (sentinel single nucleotide polymorphism [SNP] rs7412-T, β = 0.61±0.05, p-value = 3.27 × 10 −30 ) and MMP-3 (β = -0.60±0.05, p = 1.67 × 10 −32 ), as well as a completely novel pleiotropic locus at the HPX gene, associated with nine proteins. Further, the associations suggest new mechanisms of genetically mediated cardiovascular disease linked to African ancestry; we identify a novel association between variants linked to APOL1 associated chronic kidney and heart disease and the protein CKAP2 (rs73885319-G, β = 0.34±0.04, p = 1.34 × 10 −17 ) as well as an association between ATTR amyloidosis and RBP4 levels in community dwelling individuals without heart failure. Conclusions: Taken together, these results provide evidence for the functional importance of variants in non-European populations, and suggest new biological mechanisms for ancestry-specific determinants of lipids, coagulation and myocardial function.

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“…В исследовании Katz DH, et al (2021) тестировались 110 белков, взаимосвязанных с увеличением ИММЛЖ, и 13 протеинов, отражающих увеличение риска госпитализаций, связанных с ХСН, в общей популяции белой и негроидной рас [21]. Цистатин C и NT-proBNP продемонстрировали устойчивые ассоциации как с ИММЛЖ, так с риском госпитализаций, связанных с ХСН, у чернокожих и белых людей.…”

Section: Discussionunclassified

Risk of heart failure depending on the state of renal filtration function in patients with uncomplicated hypertension

Chernyavina

Козиолова

2022

Russ J Cardiol

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Aim. To assess the risk of heart failure (HF) depending on the state of renal filtration function in patients with uncomplicated hypertension (HTN) without kidney dysfunction.Material and methods. This cross-sectional screening clinical trial consecutively included 176 outpatients with uncomplicated HTN and without chronic kidney disease (CKD). To assess the HF risk, the blood concentration of N-terminal pro-brain natriuretic peptide (NT-proBNP) was determined. To assess the renal filtration function, the blood serum concentration of creatinine and cystatin C was determined, followed by glomerular filtration rate (GFR) estimation using the CKDEPI equation with both parameters. Echocardiography was performed to assess the cardiac structural and functional state.Results. Correlation analysis revealed a moderate direct relationship between NT-proBNP and blood cystatin C concentration (r=0,370; p<0,005), as well as a moderate inverse relationship with GFR (CKD-EPIcre) and GFR (CKD-EPIcys) (r= -0,321; p<0,05 and r=-0,360; p<0,005, respectively). ROC curve for all available values of blood cystatin C revealed the most optimal cut-off threshold of 1016 ng/ml (AUC=0,726, p<0,001), which ensures the sensitivity of 72,2% (p<0,001) and specificity of 62,0% (p<0,001). ROC curve for all available GFR values (CKD-EPIcys) revealed a cut-off threshold of 74 ml/min/1,73 m2 (AUC=0,702, p=0,002) with a sensitivity and specificity of 55,6% and 74,7%, respectively (p=0,001 and p=0,001, respectively). Taking into account the cut-off points for cystatin C and GFRcys, the first group consisted of 73 (41,48%) patients with cystatin C ≥1016 ng/ml and GFR (CKD-EPIcys) ≤74 ml/min/1,73 m2, while the second one — 103 (58,52%) patients with cystatin C <1016 pg/ml and GFR (CKDEPIcys) >74 ml/min/1,73 m2. The presence of impaired glucose tolerance, left ventricular diastolic dysfunction (LV DD), LV hypertrophy and left atrial enlargement leads to an additional increase in HF risk in patients with uncomplicated HNT without CKD.Conclusion. The ROC analysis showed that cystatin C and cystatin C-based GFR (CKD-EPIcys) can be used as markers of HF risk in patients with uncomplicated HTN without CKD. With an increase in cystatin C ≥1016 ng/ml, the relative risk of HF is 2,99, while with a decrease in GFR (CKD-EPIcys) ≤74 ml/min/1,73 m2 — 1,26. The presence of impaired glucose tolerance, LV DD, LV hypertrophy and left atrial enlargement in patients with uncomplicated HTN without CKD with a cystatin C increase ≥1016 ng/ml and a decrease in GFR (CKD-EPIcys) ≤74 ml/min/1,73 m2 and below further increases the risk of developing CHF.

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Multiomic Profiling in Black and White Populations Reveals Novel Candidate Pathways in Left Ventricular Hypertrophy and Incident Heart Failure Specific to Black Adults

Cited by 7 publications

References 59 publications

Large scale plasma proteomics identifies novel proteins and protein networks associated with heart failure development

Large scale plasma proteomics identifies novel proteins and protein networks associated with heart failure development

Whole Genome Sequence Analysis of the Plasma Proteome in Black Adults Provides Novel Insights Into Cardiovascular Disease

Risk of heart failure depending on the state of renal filtration function in patients with uncomplicated hypertension

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