Table 2 Characteristics of included studies
From: Proteomics for heart failure risk stratification: a systematic review
First author, year | Design | Population(s) | Enrollment | Demographics | Ejection fraction | Assay | Outcome(s) | Key findings |
|---|---|---|---|---|---|---|---|---|
Zhang[10], 2022 | Secondary analysis of a clinical trial | Derivation cohort: ATMOSPHERE trial 31 (n = 1258) | 2009–2013 | Median age: 67 (59;73), 19% female, 96% White | HFrEF (≤ 35%) | SomaScan 5 K version 3 (4076 unique proteins 5034 SOMAmers) | Primary: Composite of CV death or first HFH; Secondary: all-cause death, CV death, HFH | • 64 proteins associated with composite outcomes replicated in the validation cohort • 105 proteins associated with all-cause death • 80 proteins associated with CV death |
Validation cohort: PARADIGM-HF trial 32 (n = 1257) | 2009–2013 | Median age: 68 (61;74), 19% female, 96% White | ||||||
Gui [13], 2021 | Observational HF Registry | Derivation cohort: Henry Ford (n = 681) | 2007–2015 | Mean age: 67.9 ± 11.5, 36% female, 50.4% White | HFrEF (< 50%) | SomaScan 5 K version 4 (4111 unique proteins; 4453 SOMAmers) | Primary: All-cause death; Secondary: CV death | • 128 proteins associated with all-cause death • No report on individual proteins associated with CV death |
Validation cohort: Henry Ford (n = 336) | Mean age: 67.8 ± 12.1, 33.6% female, 48.8% White | |||||||
Cuvelliez [15], 2019 | Observational cohort (nested case–control) | INCA Study Population (n = 168) | 1998–2001 | Participants with composite outcome (n = 84): Mean age: 59 ± 11, 12% female | HFrEF (≤ 45%) | SomaScan 1.3 K version 1.2 (1305 proteins; 1310 SOMAmers) | Composite (CV death, urgent transplant, urgent assist device implantation) | • 203 proteins expressed differently between patients who died of CV causes (composite) and the patients who were alive. • |
Participants without composite outcome (n = 84); Mean age: 59 ± 10, 12% female | ||||||||
Klimczak-Tomaniak [28], 2022 | Observational cohort | Bio-SHiFT Study Population (n = 250) | 2011–2013 | Participants with composite outcome (n = 66): Mean age: 71.4 ± 19, 21% female | HFrEF (< 50%) | Olink Proteomics: Panel CVIII; 92 serially measured proteins | Composite (cardiac death, transplant, LVAD implantation, acute or worsened HF) | • 73 proteins associated with a composite outcome including cardiac death • The optimal set of biomarkers selected by LASSO included 9 proteins |
Participants without composite outcome (n = 184): Mean age: 66.2 ± 16, 28% female | ||||||||
Markousis-Mavrogenis [29], 2022 | Observational cohort | Index cohort: BIOSTAT-CHF cohort (n = 2022) | 2010–2012 | Mean age: 68.8 ± 12, 26.6% female | HFrEF (≤ 40%) HFpEF (≥ 50%) | Olink Proteomics Multiplex (Panels CVII, CVIII, Immune Response, and Oncology-II); 355 proteins | All-cause death | • 187 immune-related proteins associated with all-cause death in univariate analyses |
Validation cohort: BIOSTAT-CHF cohort (n = 1691) | Mean age: 73.7 ± 10.7, 24.1% female (based on cohort [n = 1738]) | |||||||
Ravera [30], 2022 | Observational cohort | Index cohort: BIOSTAT-CHF cohort (n = 2022) | 2010–2012 | Women group (n = 537): Mean age: 71 ± 12 Men group (n = 1485) Mean age: 67 ± 12 27% female | HFrEF (≤ 40%) HFpEF (≥ 50%) | Olink Proteomics Multiplex (Panels CVDII, CVDIII, Immune Response, and Oncology-II panels); 363 proteins | All-cause death | • 8 and 12 proteins associated with all-cause death in the index and validation cohort respectively in both men and women |
Validation cohort: BIOSTAT-CHF cohort (n = 1698) | Women group (n = 575): Mean age: 74 ± 11 Men group (n = 1123): Mean age: 73 ± 11, 34% female | |||||||
Regan [11], 2022 | Observational | CATHGEN discovery cohort (n = 176, non-HF: 88; HFpEF: 88) | 2001–2010 | Non-HF: Mean age: 53.1 ± 12.3, 42% female HFpEF: Mean age: 64.7 ± 12.3, 42% female | HFpEF (≥ 45%) | Olink 1200 Proteomics (Panels CVDII, CVDIII, Cardiometabolic, Metabolism and Development; 459 proteins | HFH and all-cause death | • 11 proteins associated with all-cause death across the 3 cohorts |
TECOS validation cohort (n = 109, non-HF:79; HFpEF: 30) | 2008–2015 | Non-HF: Mean age: 65.6 ± 8.5, 20.2% female HFpEF: Mean age:64.5 ± 8.3, 36.7% female | HFpEF (≥ 55%) |  | ||||
Jackson Heart Study cohort (all-cause death: 570; HFH: 448) | 2005–2015 | all-cause death: Mean age: 59 ± 12, 59% female HFH: Mean age: 58 ± 13, 59% female | HFpEF (≥ 50%) | Olink 1500 (Panels Cardiometabolic, CVDII, CVDIII, Cell regulation, Development, Immune, Immuno-Oncology-II, Inflammation, Metabolism, Neurology, Neuro-exploratory, Oncology II, Oncology III, Organ Damage); 369 proteins | Primary: HFH Secondary: all-cause death | |||
Ferreira [27], 2021 | Observational | Index: BIOSTAT-CHF cohort (n = 1611) | 2010–2012 |  < 65 years age group Mean age: 55 ± 8, 18.1% female 65–75 years age group Mean age: 70 ± 3, 20.4% female  > 75 years age group Mean age: 81 ± 4, 37.3% female | HFrEF (≤ 40%) | Olink technology (Panels CVDII, CVDIII, immune response, and immuno-oncology panels); 363 proteins | Primary: Composite of HFH and all-cause death Secondary: All-cause death CV death non-CV death | • 11 proteins independently associated with age and all-cause death • 6 proteins associated with age and CV death after cross-validation |
Independent validation: BIOSTAT-CHF cohort (n = 823) |  < 65 years age group Mean age: 57 ± 7, 27.6% female 65–75 years age group Mean age: 70 ± 3; 20.4% Female  > 75 years age group Mean age, 81 ± 4, 37.3% female | |||||||
Hage [16], 2017 | Observational | KaRen study biomarker substudy, no outcome group (n = 50) | 2007–2011 | ALL: Median age: 73 (66; 78) 51% female No outcome group: 73 (66; 81) 48%; female Outcome group: 74 (66; 79) 57% female | HFpEF (≥ 45%) | Olink technology Panel CVD I v1; 92 proteins | Composite (HFH or all-cause death) | • 28 biomarkers associated with composite outcome |
KaRen study biomarker substudy, outcome group (n = 36) |