Growth differentiating factor-15 and adiposity in young adults: The African-PREDICT study.

BACKGROUND AND AIMS: Circulating growth differentiation factor-15 (GDF-15) is a stress-responsive cytokine that increases in older individuals with established cardiovascular disease (CVD) and obesity. To address potential targets in primary prevention, we aimed to determine whether body weight, waist circumference, waist/height ratio, body mass index (BMI), body surface area (BSA) and leptin associate with GDF-15 in young underweight, lean and overweight/obese (ow/ob) adults. METHODS AND RESULTS: We included 1189 adults aged 20-30 years. We grouped participants as underweight (BMI ≤ 18 kg/m2, n = 59), lean (BMI > 18 kg/m2 and ≤25 kg/m2; n = 616) or ow/ob (BMI ≥ 25 kg/m2; n = 514) and determined serum GDF-15 and leptin levels. Body composition measurements, leptin and blood pressure readings were higher in the ow/ob group compared to the underweight and lean groups (all p < 0.0001). GDF-15 was higher in the underweight group compared to the lean and combined ow/ob groups (p = 0.041), and higher in obese (BMI ≥ 30 kg/m2) compared to overweight (p = 0.002) individuals. In multiple regression analysis, we found positive associations (all p ≤ 0.020) of body weight (adj. R2 = 0.398; ß = 0.11), waist circumference (adj. R2 = 0.271; ß = 0.11), waist/height ratio (adj. R2 = 0.168; ß = 0.14), BMI (adj. R2 = 0.263; ß = 0.14), BSA (adj. R2 = 0.508; ß = 0.083) and leptin (adj. R2 = 0.622; ß = 0.10) with GDF-15 in the ow/ob group. However, waist circumference (adj. R2 = 0.536; ß = -0.45), waist/height ratio (adj. R2 = 0.471; ß = -0.51) and leptin (adj. R2 = 434; ß = -0.25) associated inversely with GDF-15 in the underweight group (all p < 0.050). CONCLUSION: Our findings may suggest that in young adults with either underweight or excess adiposity, increased GDF-15 levels may contribute to the development of future cardiovascular health risks associated with pro-inflammation.

Growth differentiating factor-15 and its association with traditional cardiovascular risk factors: The African-PREDICT study.

BACKGROUND AND AIMS: Growth differentiating factor-15 (GDF-15) is a stress-induced and cardio-protective cytokine, reported to be influenced by a number of cardiovascular risk factors. In older adults, GDF-15 associated with age, black ethnicity and smoking. It is important to determine if GDF-15 could potentially be used as an early marker of cardiovascular disease, especially in young populations. We investigated whether GDF-15 associated with traditional cardiovascular risk factors (age, sex, ethnicity, blood pressure (BP), socio-economic status, waist-to-hip ratio, cholesterol, physical inactivity, smoking and alcohol use) in young apparently healthy adults. METHODS AND RESULTS: We included 1189 black and white participants (aged between 20 and 30 years). Questionnaires were used to collect demographic and physical activity data. We measured serum GDF-15, and performed 24-h ambulatory BP and pulse wave analysis. The following risk factors increased with increasing GDF-15 quartiles: age, black ethnicity, central systolic BP, 24-h diastolic BP, tumour necrosis factor-alpha, lipids, cotinine, smoking and alcohol use (all p trend ≤ 0.013). Socio-economic status and physical activity (p trend ≤ 0.014) were the lowest in the highest quartile. In multi-variable adjusted regression analyses GDF-15 associated with central systolic BP (ß = 0.076; p = 0.027), age (ß = 0.096; p = 0.006), low socio-economic status (ß = -0.12; p = 0.003), physical inactivity (ß = -0.18; p < 0.0001), tumour necrosis factor-alpha (ß = 0.28; p < 0.0001) and cotinine (ß = 0.12; p < 0.0001). CONCLUSION: In young adults, GDF-15 associated independently with multiple traditional cardiovascular risk factors including higher central systolic blood pressure, older age, lower socio-economic status, physical inactivity, inflammation and smoking. These results suggest that GDF-15 is a promising biomarker for early identification of cardiovascular risk.

Comparison of Cardiovascular Health Profiles Across Population Surveys From 5 High- to Low-Income Countries.

Background: To facilitate the shift from risk-factor management to primordial prevention of cardiovascular disease, the American Heart Association developed guidelines to score and track cardiovascular health (CVH). How the prevalence and trajectories of a high level of CVH across the life course compare among high- and lower-income countries is unknown. Methods: Nationally representative survey data with CVH variables (physical activity, cigarette smoking, body mass index, blood pressure, blood glucose, and total cholesterol levels) were identified in Ethiopia, Bangladesh, Brazil, England, and the US for adults (aged 18-69 years and not pregnant). Data were harmonized, and CVH metrics were scored using the American Heart Association guidelines, as high (2), moderate (1), or low (0), with the prevalence of high scores (better CVH) across the life course compared across countries. Results: Among 28,092 adults (Ethiopia n = 7686, 55.2% male; Bangladesh n = 6731, 48.4% male; Brazil n = 7241, 47.9% male; England n = 2691, 49.5% male, and the US n = 3743, 50.3% male), the prevalence of high CVH scores decreased as country income level increased. Declining CVH with age was universal across countries, but differences were already observable in those aged 18 years. Excess body weight appeared to be the main driver of poor CVH in higher-income countries, and the prevalence of current smoking was highest in Bangladesh. Conclusions: Our findings suggest that CVH decline with age may be universal. Interventions to promote and preserve CVH throughout the life course are needed in all populations, tailored to country-specific time courses of the decline. In countries where the level of CVH remains relatively high, protection of whole societies from risk-factor epidemics may still be feasible.

Contexte: Afin de faciliter la transition de la prise en charge des facteurs de risque vers la prévention primordiale des maladies cardiovasculaires, l'American Heart Association a élaboré des lignes directrices en vue de mesurer la santé cardiovasculaire (SCV) et d'en faire le suivi. On ignore dans quelle mesure la prévalence et la trajectoire d'un niveau élevé de SCV au cours d'une vie se comparent entre les pays à revenu élevé et les pays à plus faible revenu. Méthodologie: Des résultats de sondages représentatifs des pays concernant les variables de la SCV (activité physique, tabagisme, indice de masse corporelle, pression artérielle, glycémie et taux de cholestérol total) ont été obtenus de l'Éthiopie, du Bangladesh, du Brésil, de l'Angleterre et des États-Unis, pour des adultes âgés de 18 à 69 ans, excluant les femmes enceintes. Les données ont été harmonisées, et la SCV a été mesurée conformément aux lignes directrices de l'American Heart Association, et notée en fonction des scores suivants : élevée (2), modérée (1) ou faible (0). La prévalence de scores élevés, soit une meilleure SCV tout au long de la vie, a été comparée entre les pays. Résultats: Parmi 28 092 adultes (Éthiopie, n = 7 686, 55,2 % de sexe masculin; Bangladesh, n = 6 731, 48,4 % de sexe masculin; Brésil, n = 7 241, 47,9 % de sexe masculin; Angleterre, n = 2 691, 49,5 % de sexe masculin, et États-Unis, n = 3 743, 50,3 % de sexe masculin), la prévalence de scores correspondant à une SCV élevée diminuait à mesure que le niveau de revenu du pays augmentait. La diminution de la SCV avec l'âge était universelle dans tous les pays, mais des différences étaient déjà observables chez les personnes âgées de 18 ans. Un surplus de poids corporel semblait être le principal facteur d'une faible SCV dans les pays à revenu plus élevé; la prévalence d'un tabagisme actuel était la plus élevée au Bangladesh. Conclusions: Nos observations laissent croire que le déclin de la SCV avec l'âge pourrait être universel. Il est nécessaire de mener des interventions adaptées à la progression du déclin dans chacun des pays en vue de favoriser et de préserver la SCV tout au long de la vie, et ce, dans toutes les populations. Dans les pays où le niveau de SCV demeure relativement élevé, il pourrait être encore possible de protéger des sociétés entières contre des épidémies liées aux facteurs de risque.

Comparison of cardiovascular health profiles across population surveys from five high- to low-income countries.

Aims: With the greatest burden of cardiovascular disease morbidity and mortality increasingly observed in lower-income countries least prepared for this epidemic, focus is widening from risk factor management alone to primordial prevention to maintain high levels of cardiovascular health (CVH) across the life course. To facilitate this, the American Heart Association (AHA) developed CVH scoring guidelines to evaluate and track CVH. We aimed to compare the prevalence and trajectories of high CVH across the life course using nationally representative adult CVH data from five diverse high- to low-income countries. Methods: Surveys with CVH variables (physical activity, cigarette smoking, body mass, blood pressure, blood glucose, and total cholesterol levels) were identified in Ethiopia, Bangladesh, Brazil, England, and the United States (US). Participants were included if they were 18-69y, not pregnant, and had data for these CVH metrics. Comparable data were harmonized and each of the CVH metrics was scored using AHA guidelines as high (2), moderate (1), or low (0) to create total CVH scores with higher scores representing better CVH. High CVH prevalence by age was compared creating country CVH trajectories. Results: The analysis included 28,092 adults (Ethiopia n=7686, 55.2% male; Bangladesh n=6731, 48.4% male; Brazil n=7241, 47.9 % male; England n=2691, 49.5% male, and the US n=3743, 50.3% male). As country income level increased, prevalence of high CVH decreased (>90% in Ethiopia, >68% in Bangladesh and under 65% in the remaining countries). This pattern remained using either five or all six CVH metrics and following exclusion of underweight participants. While a decline in CVH with age was observed for all countries, higher income countries showed lower prevalence of high CVH already by age 18y. Excess body weight appeared the main driver of poor CVH in higher income countries, while current smoking was highest in Bangladesh. Conclusion: Harmonization of nationally representative survey data on CVH trajectories with age in 5 highly diverse countries supports our hypothesis that CVH decline with age may be universal. Interventions to promote and preserve high CVH throughout the life course are needed in all populations, tailored to country-specific time courses of the decline. In countries where CVH remains relatively high, protection of whole societies from risk factor epidemics may still be feasible.