JMIR Publications

ABSTRACT

Background:

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 a recent community study (CHALICE) of healthy people age 50, 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 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, the current proposal re-examines the same CHALICE participants 15 years later.

Objective:

Primary objective is to determine the predictive value of i) low plasma concentrations of the circulating cardiac hormones (ANP and BNP), and ii) high levels of the vascular hormone CNP at age 50yr, in detecting impaired cardiac and vascular function 15 years later. Secondary objectives are to determine specific associations of individual analytes (ANP, BNP, CNP, cGMP) with echo-derived changes in cardiac performance at age 50 and 65yr.

Methods:

All of the 348 participants (50% female, 15% Māori or Pacifica ethnicity) participating in the original CHALICE study – free of history of heart or renal disease at age 50yr, 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 down- stream effector (cGMP), and their bio inactive products. Humoral metabolic-cardiovascular risk factors will be measured after an overnight fast. Primary outcomes will be analysed by multiple linear regression.

Results:

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

Conclusions:

Proving our hypothesis – that low B-type Natriuretic Peptide and high C-type Natriuretic Peptide 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 to increase natriuretic hormones and reduce risk of serious cardiovascular complications using drugs already available. Such advances in detection, and from interventional corrections, have the potential not only to improve health in the community but to also reduce the high costs inevitably associated with heart failure.