Functional aging in health and heart failure: the COmPLETE Study

Abstract

Background: Cardiovascular (CV) diseases including heart failure are the leading causes of morbidity, with age being the primary risk factor. The combination of age-related organic functional impairment and reduced physical fitness can drastically impact an individual's healthspan. One's lifespan can potentially be prolonged by the preservation or improvement of physical fitness. However, it remains unclear as to which biomarkers are most suitable for distinguishing between healthy aging and the impaired organ function associated with heart failure. Therefore, a comprehensive assessment of the components of physical fitness and CV function will be performed to identify the most important factors contributing to aging in relation to both health and disease.

Methods: This cross-sectional investigation will consist of two parts: COmPLETE-Health (C-Health) and COmPLETE-Heart (C-Heart). C-Health will examine the aging trajectories of physical fitness components and CV properties in a healthy population sample aged between 20 and 100 years (n = 490). Separately, C-Heart will assess the same markers in patients at different stages of chronic heart failure (n = 80). The primary outcome to determine the difference between C-Health and C-Heart will be cardiorespiratory fitness as measured by cardiopulmonary exercise testing on a bicycle ergometer. Secondary outcomes will include walking speed, balance, isometric strength, peak power, and handgrip strength. Physical activity as a behavioural component will be assessed objectively via accelerometry. Further, CV assessments will include pulse wave velocity; retinal, arterial, and venous diameters; brachial and retinal arterial endothelial function; carotid intima-media thickness; and systolic and diastolic function. The health distances for C-Health and C-Heart will be calculated using the methodology based on statistical (Mahalanobis) distance applied to measurements of quantitative biomarkers.

Discussion: This research seeks to identify physical fitness and CV biomarkers that best resemble underlying CV risk with age. Further, it will examine which physical fitness markers are impaired most in heart failure. The presented integrative approach could define new recommendations for diagnostic guidance in aging. Ultimately, this study is expected to offer a better understanding of which functional characteristics should be specifically targeted in primary and secondary prevention to achieve an optimal healthspan.

Keywords: Aging; Exercise; Fitness; Heart failure; Vascular function.

Fig. 1

Healthspan. Healthspan is the period of life without functional limitations, chronic diseases. and disability but with a beginning loss of functional capacity symbolized by a change from green to orange colour (a). This period may be prolonged by curative medicine (b), but longer disability may also occur. Optimal healthspan can potentially be achieved by preserving or improving the functional abilities of the organism and therefore lead to a shorter period of functional limitations, chronic diseases, and disability at the end of life (c). Good physical fitness is thought to contribute essentially to optimal healthspan. Adapted from Seals et al. [7]

Fig. 2

Health distance. Graphical illustration of the health distance. Healthy individuals are potentially located at the upper limit of the healthspan (blue area). Individuals with heart failure are potentially located at the lower limit of the healthspan (red area) and reaching the line of functional limitation (grey line) earlier as compared with healthy individuals. Double arrows denote the health distance between healthy individuals and patients with chronic heart failure. The upper bar chart represents the better components of physical fitness of healthy individuals, while the lower bar chart represents the worse components of physical fitness of a patient with chronic heart failure. Modified from Seals et al. [7]