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. 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. 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.

As ageing is a major risk factor for the development of non-communicable diseases, extending healthspan has become a medical and societal necessity. Precise lipid phenotyping that captures metabolic individuality could support healthspan extension strategies. This study applied ‘omic-scale lipid profiling to characterise sex-specific age-related differences in the serum lipidome composition of healthy humans. A subset of the COmPLETE-Health study, composed of 73 young (25.2 ± 2.6 years, 43% female) and 77 aged (73.5 ± 2.3 years, 48% female) clinically healthy individuals, was investigated, using an untargeted liquid chromatography high-resolution mass spectrometry approach. Compared to their younger counterparts, aged females and males exhibited significant higher levels in 138 and 107 lipid species representing 15 and 13 distinct subclasses, respectively. Percentage of difference ranged from 5.8% to 61.7% (females) and from 5.3% to 46.0% (males), with sphingolipid and glycerophophospholipid species displaying the greatest amplitudes. Remarkably, specific sphingolipid and glycerophospholipid species, previously described as cardiometabolically favourable, were found elevated in aged individuals. Furthermore, specific ether-glycerophospholipid and lyso-glycerophosphocholine species displayed higher levels in aged females only, revealing a more favourable lipidome evolution in females. Altogether, age determined the circulating lipidome composition, while lipid species analysis revealed additional findings that were not observed at the subclass level.

Purpose: Accelerometer-assessed physical activity (PA) can be summarized using cut-point–free or population-specific cut-point–based outcomes. We aimed to 1) examine the interrelationship between cut-point–free (intensity gradient (IG) and average acceleration (AvAcc)) and cut-point–based accelerometer metrics, 2) compare the association between cardiorespiratory fitness (CRF) and cut-point–free metrics to that with cut-point–based metrics in healthy adults aged 20 to 89 yr and patients with heart failure, and 3) provide age-, sex-, and CRF-related reference values for healthy adults. Methods: In the COmPLETE study, 463 healthy adults and 67 patients with heart failure wore GENEActiv accelerometers on their nondominant wrist and underwent cardiopulmonary exercise testing. Cut-point–free (IG: distribution of intensity of activity across the day; AvAcc: proxy of volume of activity) and traditional (moderate-to-vigorous and vigorous activity) metrics were generated. The “interpretablePA” R-package was developed to translate findings into clinical practice. Results: IG and AvAcc yield complementary information on PA with both IG (P = 0.009) and AvAcc (P < 0.001) independently associated with CRF in healthy individuals (adjusted R ² = 73.9%). Only IG was independently associated with CRF in patients with heart failure (P = 0.043, adjusted R ² = 38.4%). The best cut-point–free and cut-point–based model had similar predictive value for CRF in both cohorts. We produced age- and sex-specific reference values and percentile curves for IG, AvAcc, moderate-to-vigorous PA, and vigorous PA for healthy adults. Conclusions: IG and AvAcc are strongly associated with CRF and thus indirectly with the risk of noncommunicable diseases and mortality, in healthy adults and patients with heart failure. However, unlike cut-point–based metrics, IG and AvAcc are comparable across populations. Our reference values provide a healthy age- and sex-specific comparison that may enhance the translation and utility of cut-point–free metrics in clinical practice.

Background: For valid accelerometer-assessed physical activity (PA) data, several methodological aspects should be considered. We aimed to 1) visualize the applicability of absolute accelerometer cut-offs to classify PA intensity, 2) verify recommendations to measure PA over 7 days by examining inter-day variability and reactivity, 3) examine seasonal differences in PA, and 4) recommend during which 10 h day period accelerometers should be worn to capture the most PA in patients with heart failure (HEART) and healthy individuals (HEALTH).Methods: Fifty-six HEART (23% female; mean age 66 ± 13 years) and 299 HEALTH (51% female; mean age 54 ± 19 years) of the COmPLETE study wore accelerometers for 14 days. Aim 1 was analyzed descriptively. Key analyses were performed using linear mixed models.Results: The results yielded poor applicability of absolute cut-offs. The day of the week significantly affected PA in both groups. PA-reactivity was not present in either group. A seasonal influence on PA was only found in HEALTH. Large inter-individual variability in PA timing was present.Conclusions: Our data indicated that absolute cut-offs foster inaccuracies in both populations. In HEART, Sunday and four other days included in the analyses seem sufficient to estimate PA and the consideration of seasonal differences and reactivity seems not necessary. For healthy individuals, both weekend days plus four other days should be integrated into the analyses and seasonal differences should be considered. Due to substantial inter-individual variability in PA timing, accelerometers should be worn throughout waking time. These findings may improve future PA assessment.Trial registration: The COmPLETE study was registered at clinicaltrials.gov (NCT03986892).

Objective: To (1) establish extensive physiological profiles of highly trained CrossFit® athletes using gold-standard tests and (2) investigate which physiological markers best correlate with CrossFit Open performance. Methods: This study encompassed 60 participants (30 men and 30 women), all within the top 5% of the CrossFit Open, including 7 CrossFit semifinalists and 3 CrossFit Games finalists. Isokinetic dynamometers were employed to measure maximum isometric and isokinetic leg and trunk strength. Countermovement-jump height and maximum isometric midthigh-pull strength were assessed on a force plate. Peak oxygen uptake (VO₂peak) was measured by a cardiopulmonary exercise test, and critical power and W′ were evaluated during a 3-minute all-out test, both on a cycle ergometer. Results: Male and female athletes’ median (interquartile range) VO₂peak was 4.64 (4.43, 4.80) and 3.21 (3.10, 3.29) L·min⁻¹, critical power 314.5 (285.9, 343.6) and 221.3 (200.9, 238.9) W, and midthigh pull 3158 (2690, 3462) and 2035 (1728, 2347) N. Linear-regression analysis showed strong evidence for associations between different anthropometric variables and CrossFit Open performance in men and women, whereas for markers of cardiorespiratory fitness such as VO₂peak, this was only true for women but not men. Conventional laboratory evaluations of strength, however, manifested minimal evidence for associations with CrossFit Open performance across both sexes. Conclusions: This study provides the first detailed insights into the physiology of high-performing CrossFit athletes and informs training optimization. Furthermore, the results emphasize the advantage of athletes with shorter limbs and suggest potential modifications to CrossFit Open workout designs to level the playing field for athletes across different anthropometric characteristics.

Background: To investigate whether quantifying both the absolute and relative intensity of physical activity (PA) improves understanding of age, sex, and occupation-related differences in PA in healthy adults aged 20–89. Methods: In the cross-sectional COmPLETE study, participants (N = 460, 48% women, age 55 [IQR 37, 71]) wore accelerometers for up to 14 days and underwent cardiopulmonary exercise testing. Average acceleration (AvAcc) and distribution of intensity (IG) of PA across the day were expressed in absolute terms (__ABS) and relative (__REL) to the acceleration at the individual´s maximum intensity, predicted from cardiorespiratory fitness. Results: After initial increases, AvAcc__ABS and IG__ABS continuously declined beyond age 40–45, whereas AvAcc__REL and IG__REL increased until stabilising at age ~ 70 and declining at age ~ 60, respectively. Cardiorespiratory fitness constantly declined. Women had trivially higher AvAcc__ABS and moderately higher AvAcc__REL, but not IG__ABS and IG_{_REL}, than men. Occupations involving at least moderate PA showed higher AvAcc__ABS and AvAcc__REL, but not IG__ABS and IG_{_REL} indicating longer periods of low-intensity PA, compared to sitting/standing occupations. Conclusions: Distinct age trajectories of absolute and relative metrics as well as cardiorespiratory fitness suggest that the age-related decline in the latter preceded that of PA. Women’s higher AvAcc__ABS and AvAcc__REL relate to more low-intensity PA combined with lower cardiorespiratory fitness rather than more health-enhancing higher-intensity PA. Finally, the intensity profile of occupational PA may provide insight into why occupational PA appears to lack a prophylactic association with health. Quantifying both the absolute and relative intensity of accelerometer-assessed PA provides greater insight than either alone. Trial registration: On clinicaltrials.gov (NCT03986892). Retrospectively registered 14 June 2019.