+1 Recommend
1 collections

      To submit your manuscript, please click here

      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      The Predictive Value of A, B, and C-Type Natriuretic Peptides in People at Risk of Heart Disease: Protocol for a Longitudinal Observational Study


      Read this article at

          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.



          Heart disease and stroke are major and often unheralded causes of serious morbidity and premature death in middle age. Early detection of those most at risk is an urgent unmet need for instituting preventative measures. In an earlier community study (Canterbury Health, Ageing and Life Course [CHALICE]) of healthy people aged 50 years, contrary to previous reports, low levels of the heart hormone B-type natriuretic peptide (BNP) were associated with reduced measures of heart function and higher markers of vascular risk. A specific gene variant (rs198358) was found to be an independent contributor to higher BNP levels. A closely related vascular hormone (C-type natriuretic peptide [CNP]) showed opposite associations—higher levels were correlated with higher vascular risk and reduced cardiac function. To determine whether these novel findings predict serious heart or vascular disease in later life, this proposal re-examines the same CHALICE participants 15 years later.


          The primary objective is to determine the predictive value of (1) low plasma concentrations of the circulating cardiac hormones (atrial natriuretic peptide [ANP] and BNP) and (2) high levels of the vascular hormone CNP at age 50 years in detecting impaired cardiac and vascular function 15 years later. Secondary objectives are to determine specific associations of individual analytes (ANP, BNP, CNP, cyclic guanosine monophosphate [cGMP]) with echo-derived changes in cardiac performance at ages 50 years and 65 years.


          All of the 348 participants (205/348, 58.9% female; 53/348, 15.2% Māori or Pacifica ethnicity) participating in the original CHALICE study—free of history of heart or renal disease at age 50 years and who consented to further study—will be contacted, recruited, and restudied as previously described. Data will include intervening health history, physical examination, heart function (speckle-tracking echocardiography), vascular status (carotid intimal thickness), and genetic status (genome-wide genotyping). Laboratory measures will include fasting blood sampling and routine biochemistry, ANP, BNP, CNP, their downstream effector (cGMP), and their bio-inactive products. Humoral metabolic-cardiovascular risk factors will be measured after an overnight fast. Primary outcomes will be analyzed using multiple linear regression.


          The study will commence in 2022 and be completed in 2024.


          Proving our hypothesis—that low BNP and high CNP at any age in healthy people predict premature aging of heart and blood vessels, respectively—opens the way to early detection and improved outcomes for those most at risk. Confirmation of our hypotheses would improve current methods of screening and, in appropriate cases, enable interventions aimed at increasing natriuretic hormones and reducing risk of serious cardiovascular complications using drugs already available. Such advances in detection, and from interventional corrections, have the potential to not only improve health in the community but also reduce the high costs inevitably associated with heart failure.

          International Registered Report Identifier (IRRID)


          Related collections

          Most cited references77

          • Record: found
          • Abstract: found
          • Article: not found

          The changing landscape of atherosclerosis

          Emerging evidence has spurred a considerable evolution of concepts relating to atherosclerosis, and has called into question many previous notions. Here I review this evidence, and discuss its implications for understanding of atherosclerosis. The risk of developing atherosclerosis is no longer concentrated in Western countries, and it is instead involved in the majority of deaths worldwide. Atherosclerosis now affects younger people, and more women and individuals from a diverse range of ethnic backgrounds, than was formerly the case. The risk factor profile has shifted as levels of low-density lipoprotein (LDL) cholesterol, blood pressure and smoking have decreased. Recent research has challenged the protective effects of high-density lipoprotein, and now focuses on triglyceride-rich lipoproteins in addition to low-density lipoprotein as causal in atherosclerosis. Non-traditional drivers of atherosclerosis-such as disturbed sleep, physical inactivity, the microbiome, air pollution and environmental stress-have also gained attention. Inflammatory pathways and leukocytes link traditional and emerging risk factors alike to the altered behaviour of arterial wall cells. Probing the pathogenesis of atherosclerosis has highlighted the role of the bone marrow: somatic mutations in stem cells can cause clonal haematopoiesis, which represents a previously unrecognized but common and potent age-related contributor to the risk of developing cardiovascular disease. Characterizations of the mechanisms that underpin thrombotic complications of atherosclerosis have evolved beyond the 'vulnerable plaque' concept. These advances in our understanding of the biology of atherosclerosis have opened avenues to therapeutic interventions that promise to improve the prevention and treatment of now-ubiquitous atherosclerotic diseases.
            • Record: found
            • Abstract: not found
            • Article: not found

            Identification, Inference and Sensitivity Analysis for Causal Mediation Effects

              • Record: found
              • Abstract: not found
              • Article: not found

              Genome-wide association studies


                Author and article information

                JMIR Res Protoc
                JMIR Res Protoc
                JMIR Research Protocols
                JMIR Publications (Toronto, Canada )
                11 January 2023
                : 12
                : e37011
                [1 ] Christchurch Heart Institute Department of Medicine University of Otago Christcurch New Zealand
                [2 ] Department of Pathology and Biomedical Science University of Otago Christchurch New Zealand
                [3 ] Biostatistics and Computational Biology Unit University of Otago Christchurch New Zealand
                Author notes
                Corresponding Author: Timothy C R Prickett tim.prickett@ 123456otago.ac.nz
                Author information
                ©Timothy C R Prickett, John F Pearson, Richard W Troughton, Martin A Kennedy, Eric A Espiner. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 11.01.2023.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, first published in JMIR Research Protocols, is properly cited. The complete bibliographic information, a link to the original publication on https://www.researchprotocols.org, as well as this copyright and license information must be included.

                : 2 February 2022
                : 30 November 2022
                : 12 December 2022
                : 13 December 2022

                cardiovascular risk,arterial and lv elastance,polygenic risk scores,cgmp,bioactive and amino-terminal natriuretic peptide,heart disease,cardiovascular,middle age,risk,prediction,biomarkers,detection


                Comment on this article