A comparison of echocardiographic and circulating cardiac biomarkers for predicting incident cardiovascular disease

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Abstract

Background

Echocardiographic measures are known predictors of cardiovascular disease (CVD) in the general population. This study compared the predictive value of such measures to that of circulating cardiac biomarkers for a composite cardiovascular disease outcome in an aging population.

Methods

In this prospective population-based cohort study, echocardiography was performed at baseline together with assessments of traditional CVD risk factors and circulating cardiac biomarkers, NT-proBNP and troponin I, in 1016 individuals all aged 70 years. Assessments were repeated at ages 75 and 80. A composite CVD outcome (myocardial infarction, heart failure or ischemic stroke) was charted over 15 years. All echocardiography variables, except for the E/A ratio, were analyzed on a continuous scale.

Results

Over 10 years, left atrial (LA) diameter, left ventricular mass index (LVMI) and high E/A ratio (>1.5) increased, while left ventricular ejection fraction (LVEF) remained unchanged. Using Cox proportional hazard analyses with time-updated variables for echocardiographic measures and traditional risk factors, an enlarged LA diameter and a low LVEF were independently related to incident CVD in 222 participants. The addition of LA diameter and LVEF to traditional risk factors increased the C-statistic by 1.5% (p = 0.008). However, the addition of troponin I and NT-proBNP to traditional risk factors increased the C-statistic by 3.0% (p<0.001).

Conclusion

An enlarged LA diameter and a low LVEF improved the prediction of incident CVD compared to traditional risk factors. However, given that troponin I and NT-proBNP improved prediction to a similar extent, the use of simple blood tests to improve clinical cardiovascular disease risk prediction is only further supported by this study.

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Most cited references 28

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Estimating glomerular filtration rate from serum creatinine and cystatin C.

Lesley A. Inker, Christopher H. Schmid, Hocine Tighiouart … (2012)

Estimates of glomerular filtration rate (GFR) that are based on serum creatinine are routinely used; however, they are imprecise, potentially leading to the overdiagnosis of chronic kidney disease. Cystatin C is an alternative filtration marker for estimating GFR. Using cross-sectional analyses, we developed estimating equations based on cystatin C alone and in combination with creatinine in diverse populations totaling 5352 participants from 13 studies. These equations were then validated in 1119 participants from 5 different studies in which GFR had been measured. Cystatin and creatinine assays were traceable to primary reference materials. Mean measured GFRs were 68 and 70 ml per minute per 1.73 m(2) of body-surface area in the development and validation data sets, respectively. In the validation data set, the creatinine-cystatin C equation performed better than equations that used creatinine or cystatin C alone. Bias was similar among the three equations, with a median difference between measured and estimated GFR of 3.9 ml per minute per 1.73 m(2) with the combined equation, as compared with 3.7 and 3.4 ml per minute per 1.73 m(2) with the creatinine equation and the cystatin C equation (P=0.07 and P=0.05), respectively. Precision was improved with the combined equation (interquartile range of the difference, 13.4 vs. 15.4 and 16.4 ml per minute per 1.73 m(2), respectively [P=0.001 and P 30% of measured GFR, 8.5 vs. 12.8 and 14.1, respectively [P<0.001 for both comparisons]). In participants whose estimated GFR based on creatinine was 45 to 74 ml per minute per 1.73 m(2), the combined equation improved the classification of measured GFR as either less than 60 ml per minute per 1.73 m(2) or greater than or equal to 60 ml per minute per 1.73 m(2) (net reclassification index, 19.4% [P<0.001]) and correctly reclassified 16.9% of those with an estimated GFR of 45 to 59 ml per minute per 1.73 m(2) as having a GFR of 60 ml or higher per minute per 1.73 m(2). The combined creatinine-cystatin C equation performed better than equations based on either of these markers alone and may be useful as a confirmatory test for chronic kidney disease. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases.).

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Prognostic implications of echocardiographically determined left ventricular mass in the Framingham Heart Study.

Bradley R Garrison, W Kannel, Daniel Savage … (1990)

A pattern of left ventricular hypertrophy evident on the electrocardiogram is a harbinger of morbidity and mortality from cardiovascular disease. Echocardiography permits the noninvasive determination of left ventricular mass and the examination of its role as a precursor of morbidity and mortality. We examined the relation of left ventricular mass to the incidence of cardiovascular disease, mortality from cardiovascular disease, and mortality from all causes in 3220 subjects enrolled in the Framingham Heart Study who were 40 years of age or older and free of clinically apparent cardiovascular disease, in whom left ventricular mass was determined echocardiographically. During a four-year follow-up period, there were 208 incident cardiovascular events, 37 deaths from cardiovascular disease, and 124 deaths from all causes. Left ventricular mass, determined echocardiographically, was associated with all outcome events. This relation persisted after we adjusted for age, diastolic blood pressure, pulse pressure, treatment for hypertension, cigarette smoking, diabetes, obesity, the ratio of total cholesterol to high-density lipoprotein cholesterol, and electrocardiographic evidence of left ventricular hypertrophy. In men, the risk factor-adjusted relative risk of cardiovascular disease was 1.49 for each increment of 50 g per meter in left ventricular mass corrected for the subject's height (95 percent confidence interval, 1.20 to 1.85); in women, it was 1.57 (95 percent confidence interval, 1.20 to 2.04). Left ventricular mass (corrected for height) was also associated with the incidence of death from cardiovascular disease (relative risk, 1.73 [95 percent confidence interval, 1.19 to 2.52] in men and 2.12 [95 percent confidence interval, 1.28 to 3.49] in women). Left ventricular mass (corrected for height) was associated with death from all causes (relative risk, 1.49 [95 percent confidence interval, 1.14 to 1.94] in men and 2.01 [95 percent confidence interval, 1.44 to 2.81] in women). We conclude that the estimation of left ventricular mass by echocardiography offers prognostic information beyond that provided by the evaluation of traditional cardiovascular risk factors. An increase in left ventricular mass predicts a higher incidence of clinical events, including death, attributable to cardiovascular disease.

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The validity of a diagnosis of heart failure in a hospital discharge register.

Johan Sundström, Johan Ärnlöv, Erik Ingelsson … (2005)

The accuracy of a diagnosis of heart failure (HF) in hospital discharge registers is largely unknown. We aimed to determine the validity of such a diagnosis in the Swedish hospital discharge register. In a population-based study of 2322 middle-aged men (the ULSAM study), 321 participants were diagnosed with HF according to the Swedish hospital discharge register, during a median follow-up time of 29 years. A review board examined the validity of the diagnosis according to the European Society of Cardiology definition of HF. Eighty-two percent of the possible cases were classified as having definite HF. An echocardiographic examination increased the validity to 88%. For patients treated at an internal medicine or cardiology clinic the validity was 86% and 91%, respectively. If HF was the primary diagnosis, the validity was 95%, irrespective of clinic type. The HF diagnosis in the Swedish hospital discharge register appears slightly less precise than for acute myocardial infarction and stroke. For population-based research, only those with a primary diagnosis of HF in the hospital discharge register should be regarded as definite HF cases, or alternatively the cases should be validated individually.

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Author and article information

Contributors

Lars Lind: Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SupervisionRole: Writing – original draftRole: Writing – review & editing

Jordan Loader:

ORCID: https://orcid.org/0000-0001-5623-7478

Role: Writing – original draftRole: Writing – review & editing

Bertil Lindahl: Role: Formal analysisRole: MethodologyRole: Writing – original draftRole: Writing – review & editing

Kai M. Eggers: Role: Formal analysisRole: MethodologyRole: Writing – original draftRole: Writing – review & editing

Johan Sundström: Role: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Writing – original draftRole: Writing – review & editing

Chengming Fan: Role: Editor

Journal

Journal ID (nlm-ta): PLoS One

Journal ID (iso-abbrev): PLoS One

Journal ID (publisher-id): plos

Title: PLoS ONE

Publisher: Public Library of Science (San Francisco, CA USA )

ISSN (Electronic): 1932-6203

Publication date (Electronic): 25 July 2022

Publication date Collection: 2022

Volume: 17

Issue: 7

Electronic Location Identifier: e0271835

Affiliations

[1 ] Department of Medical Sciences, Uppsala University, Uppsala, Sweden

[2 ] Inserm U1300 –HP2, Université Grenoble Alpes, CHU Grenoble Alpes, Grenoble, France

[3 ] The George Institute for Global Health, University of New South Wales, Sydney, Australia

Second Xiangya Hospital, CHINA

Author notes

Competing Interests: The authors have declared that no competing interests exist.

* E-mail: johan.sundstrom@ 123456medsci.uu.se

Author information

Jordan Loader https://orcid.org/0000-0001-5623-7478

Article

Publisher ID: PONE-D-22-12354

DOI: 10.1371/journal.pone.0271835

PMC ID: 9312363

PubMed ID: 35877671

SO-VID: 708df4f7-ad4d-4c33-9613-8e08ee7f9e99

License:

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

History

Date received : 27 April 2022

Date accepted : 7 July 2022

Page count

Figures: 2, Tables: 4, Pages: 16

Funding

Funded by: funder-id http://dx.doi.org/10.13039/100010665, H2020 Marie Skłodowska-Curie Actions;

Award ID: 898829

Award Recipient :

ORCID: https://orcid.org/0000-0001-5623-7478

Jordan Loader

J.L. has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement no. 898829. https://ec.europa.eu. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Data Availability Due to Swedish laws on personal integrity and health data, as well as the Ethics Committee, we are not allowed to make any data included health variables open to the public even if made anonymous. The data could be shared with other researchers after a request to the head of our department ( eva.lindberg@ 123456medsci.uu.se ).

A comparison of echocardiographic and circulating cardiac biomarkers for predicting incident cardiovascular disease

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Abstract

Background

Methods

Results

Conclusion

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Journal of Circulating Biomarkers

Most cited references 28

Estimating glomerular filtration rate from serum creatinine and cystatin C.

Prognostic implications of echocardiographically determined left ventricular mass in the Framingham Heart Study.

The validity of a diagnosis of heart failure in a hospital discharge register.

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