Evaluation of Temporal Changes in Cardiovascular Biomarker Concentrations Improves Risk Prediction in an Elderly Population from the Community

Eggers, Kai M.; Kempf, Tibor; Larsson, Anders; Lindahl, Bertil; Wallentin, Lars; Wollert, Kai C.; Lind, Lars

doi:10.1373/clinchem.2015.246876

Cited by 18 publications

(18 citation statements)

References 37 publications

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“…The longitudinal evolution of the biomarkers via joint modeling showed a stronger positive association of GDF-15 with death from CHD and HF than the single biomarker measurements. Related to our findings, Eggers et al found that baseline concentrations of GDF-15 could predict future CVD events and especially all-cause mortality in an elderly community-dwelling population [ 26 ]. In detail, changes over the time of GDF-15 predicted individual´s all-cause mortality, whereas GDF-15 and cardiovascular events displayed no significant association [ 26 ].…”

Section: Discussionsupporting

confidence: 83%

“…Interestingly, in this community-dwelling cohort with 3,428 participants GDF-15 as well as the other biomarkers soluble ST2 (sST2) and high-sensitivity troponin I (hsTnI) did not predict coronary artery disease events, but total mortality [ 18 ]. Notable, in some of the previous described community-dwelling cohorts participants were elderly individuals with a higher-risk of developing CVD events and HF [ 15 , 17 , 26 ]. In comparison, the Dan-MONICA cohort represents a middle-aged cohort which is more similar to the Dallas Heart Study [ 16 ].…”

Section: Discussionmentioning

confidence: 99%

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Predictive value of long-term changes of growth differentiation factor-15 over a 27-year-period for heart failure and death due to coronary heart disease

et al. 2018

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BackgroundGrowth differentiation factor-15 (GDF-15), Cystatin C and C-reactive protein (CRP) have been discussed as biomarkers for prediction of cardiac diseases. The aim of this study was to investigate the predictive value of single and repeated measurements of GDF-15 compared to Cystatin C and CRP for incidence of heart failure (HF) and death due to coronary heart disease (CHD) in the general population.Methods and resultsLevels of GDF-15, CRP and Cystatin C were determined in three repeated measurements collected 5 years apart in the DAN-MONICA (Danish-Multinational MONitoring of trends and determinants in Cardiovascular disease) cohort (participants at baseline n = 3785). Cox regression models adjusted for cardiovascular risk factors revealed significantly increased hazard ratios (HR) for GDF-15 for incident HF 1.36 (HR per interquartile range (IQR) increase, 95% confidence interval (CI): 1.16; 1.59) and for death from CHD 1.51 (HR per IQR increase, 95% CI: 1.31, 1.75) (both with p<0.001). Joint modeling of time-to-event and longitudinal GDF-15 over a median 27-year follow-up period showed that the marker evolution was positively associated with death of CHD (HR per IQR increase 3.02 95% CI: (2.26, 4.04), p < 0.001) and HF (HR per IQR increase 2.12 95% CI: (1.54, 2.92), p<0.001). However using Cox models with follow-up time starting at the time of the third examination, serial measurement of GDF-15, modeled as changes between the measurements, did not improve prediction over that of the most recent measurement.ConclusionsGDF-15 is a promising biomarker for prediction of HF and death due to CHD in the general population, which may provide prognostic information to already established clinical biomarkers. Repeated measurements of GDF-15 displayed only a slight improvement in the prediction of these endpoints compared to a single measurement.

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Section: Discussionsupporting

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Predictive value of long-term changes of growth differentiation factor-15 over a 27-year-period for heart failure and death due to coronary heart disease

et al. 2018

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“…Prior studies of associations of protein levels with changes in body weight or fat distribution during aging have typically focused on one or a few proteins and typically on well‐studied biomarkers, such as C‐reactive protein, interleukin‐6, N‐terminal pro‐B‐type natriuretic peptide, and troponin I . In the present study, we evaluated for the first time whether changes of a large number of proteins between ages 70 and 80 were related to changes in measures of body weight and fat distribution during the same time period.…”

Section: Discussionmentioning

confidence: 97%

Changes in Proteomic Profiles are Related to Changes in BMI and Fat Distribution During 10 Years of Aging

Lind

Figarska

Sundström

et al. 2019

Obesity

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Objective This study investigated how changes in 84 proteins over a 10‐year period of aging were related to changes in measures of body fat and distribution over the same period. Methods Cardiovascular candidate proteins were measured using the proximal extension assay technique, along with BMI and waist‐hip ratio (WHR), at ages 70, 75, and 80 in 1,016 participants of the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) cohort. Associations of changes in plasma protein levels, BMI, and WHR over time were analyzed using linear mixed models. Results Changes in 19 and 16 proteins were significantly associated with changes in BMI and WHR, respectively (P < 0.00059), over the investigated 10‐year period. Leptin and fatty acid‐binding protein 4 were among the proteins most strongly associated with changes in both BMI and WHR. Four of the proteins significantly tracked with change in BMI (P < 0.00059) but not WHR (P > 0.05): endothelial cell‐specific molecule 1, pentraxin‐related protein PTX3, ST2 protein (also known as interleukin‐1 receptor‐like 1), and spondin‐1. Five proteins tracked with change in WHR (P < 0.00059) but not BMI (P > 0.05): caspase‐8, cathepsin L1, oxidized low‐density lipoprotein receptor 1, interleukin‐6 receptor subunit alpha, and C‐C motif chemokine 20. Conclusions This is the first large longitudinal study of how changes in plasma protein signatures are associated with changes in measures of body fat and distribution over 10 years of aging.

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“…Indeed, in HF patients volume overload is frequently associated to other comorbidities, including bad lifestyle, aging, systemic abnormalities (renal impairment for example), but also bad lifestyle, aging. 31 Interestingly, it has been reported in general population that poor health behaviours (smoking habits, inactivity, nutritional disorders …) and presence of modifiable cardiovascular risk factors (high blood pressure, cholesterol, glucose intolerance, and obesity) are associated with high levels of GDF-15. 39 In addition, in a cohort of 324 same-sex twins, it has been shown that half of the variation in GDF-15 could be attributed to individual-specific environmental influences.…”

Section: Additional Values Of Biomarkers Over Timementioning

confidence: 99%

Multimarker approach including CRP, sST2 and GDF‐15 for prognostic stratification in stable heart failure

et al. 2020

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Aims Inflammation and cardiac remodelling are common and synergistic pathways in heart failure (HF). Emerging biomarkers such as soluble suppression of tumorigenicity 2 (sST2) and growth differentiation factor-15 (GDF-15), which are linked to inflammation and fibrosis process, have been proposed as prognosis factors. However, their potential additive values remain poorly investigated. Methods and results Here, we aimed at evaluating inflammatory and remodelling biomarkers to predict both short-term and long-term mortality in a population with chronic HF in comparison with other classical clinical or biological markers (i.e. N terminal pro brain natriuretic peptide, hs-cTnT, C-reactive protein) alone or using meta-analysis global group in chronic HF risk score in a cohort of 182 patients followed during 80 months (interquartile range: 12.3-90.0). Proportional hazard assumption does not hold for sST2 and C-reactive protein, and follow-up was split into short term (less than 1 year), midterm (between 1 and 5 years), and long term (after 5 years). In univariate analysis, C-reactive protein and sST2 were predictive of short-term mortality but not of middle term and long term whereas GDF-15 was predictive of short and mid-term but not of long-term mortality. In a multivariate model after adjustment for meta-analysis global group in chronic HF score including the three markers, only sST2 was predictive of short-term mortality (P = 0.0225), and only GDF-15 was predictive of middle term mortality (P = 0.0375). None of the markers was predictive of long-term mortality. Conclusions Our results demonstrate that both sST2 and GDF-15 significantly improve the prognosis evaluation of HF patients and suggest that the value of GDF-15 is more sustained overtime and could predict middle term events.

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Evaluation of Temporal Changes in Cardiovascular Biomarker Concentrations Improves Risk Prediction in an Elderly Population from the Community

Abstract: BACKGROUND:There is increasing interest in measurements of cardiovascular (CV) biomarker concentrations for risk prediction in the general population. We investigated the prognostic utility of a panel of novel CV biomarkers including biomarker changes over time.

Cited by 18 publications

References 37 publications

Predictive value of long-term changes of growth differentiation factor-15 over a 27-year-period for heart failure and death due to coronary heart disease

Predictive value of long-term changes of growth differentiation factor-15 over a 27-year-period for heart failure and death due to coronary heart disease

Changes in Proteomic Profiles are Related to Changes in BMI and Fat Distribution During 10 Years of Aging

Multimarker approach including CRP, sST2 and GDF‐15 for prognostic stratification in stable heart failure

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