Prickett Timothy C R, Pearson John F, Troughton Richard W, Kennedy Martin A, Espiner Eric A
Christchurch Heart Institute, Department of Medicine, University of Otago, Christcurch, New Zealand.
Department of Pathology and Biomedical Science, University of Otago, Christchurch, New Zealand.
JMIR Res Protoc. 2023 Jan 11;12:e37011. doi: 10.2196/37011.
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): PRR1-10.2196/37011.
心脏病和中风是导致中年人群严重发病和过早死亡的主要原因，且常常没有先兆。尽早发现高危人群是采取预防措施的一项迫切未满足需求。在一项针对50岁健康人群的早期社区研究（坎特伯雷健康、衰老与生命历程研究[CHALICE]）中，与之前的报道相反，心脏激素B型利钠肽（BNP）水平较低与心脏功能指标降低以及血管风险标志物升高有关。发现一种特定的基因变异（rs198358）是BNP水平升高的一个独立影响因素。一种密切相关的血管激素（C型利钠肽[CNP]）呈现出相反的关联——较高水平与较高的血管风险和降低的心脏功能相关。为了确定这些新发现是否能预测晚年严重的心脏或血管疾病，本研究在15年后对CHALICE研究的同一批参与者进行重新检查。
主要目的是确定（1）50岁时循环心脏激素（心房利钠肽[ANP]和BNP）的低血浆浓度以及（2）血管激素CNP的高水平在检测15年后心脏和血管功能受损方面的预测价值。次要目的是确定个体分析物（ANP、BNP、CNP、环磷酸鸟苷[cGMP]）与50岁和65岁时超声心动图得出的心脏性能变化之间的具体关联。
将联系、招募并重新研究参与原始CHALICE研究的所有348名参与者（205/348，58.9%为女性；53/348，15.2%为毛利族或太平洋岛民），他们在50岁时无心脏病或肾病病史且同意进一步研究。数据将包括期间的健康史、体格检查、心脏功能（斑点追踪超声心动图）、血管状况（颈动脉内膜厚度）和基因状况（全基因组基因分型）。实验室检测将包括空腹采血及常规生化检查、ANP、BNP、CNP、它们的下游效应物（cGMP）及其生物无活性产物。体液代谢 - 心血管危险因素将在禁食过夜后进行测量。主要结局将采用多元线性回归分析。
该研究将于2022年开始并于2024年完成。
证明我们的假设——健康人群在任何年龄时BNP水平低和CNP水平高分别预示心脏和血管过早衰老——为高危人群的早期发现和改善结局开辟了道路。对我们假设的证实将改进当前的筛查方法，并在适当情况下，使用现有药物进行旨在增加利钠激素和降低严重心血管并发症风险的干预。检测方面的这些进展以及干预性纠正措施不仅有可能改善社区健康，还能降低与心力衰竭不可避免相关的高昂成本。
国际注册报告识别码（IRRID）：PRR1 - 10.2196/37011。
