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Large artery stiffness is associated with marinobufagenin in young adults: the African-PREDICT study.

ABSTRACT: OBJECTIVES:The cardiotonic steroid, marinobufagenin (MBG), has been shown to play a physiological natriuretic role in response to salt intake. However, recent studies in clinical and animal models demonstrated possible links between elevated levels of endogenous MBG and increased arterial stiffness. Large artery stiffness is a known predictor of future cardiovascular disease. We, therefore, investigated whether large artery stiffness relates to 24-h urinary MBG excretion in young apparently healthy black and white adults. METHODS:This study included data of 711 participants (black 51%, men 42%, mean age 24.8?±?3.02 years). We measured the carotid-femoral pulse wave velocity (cfPWV), 24-h urinary MBG and sodium excretion. RESULTS:In single, partial and multivariable adjusted (Adj.) regression analyses, we found a persistent positive association between cfPWV and MBG excretion in women [Adj. R?=?0.23; standardized (std.) ??=?0.15; P?=?0.002], but not men (Adj. R?=?0.17; std. ??=?0.06; P?=?0.31). Multiple regression models were adjusted for ethnicity, age, waist-to-height ratio, mean arterial pressure, high-density lipoprotein cholesterol, C-reactive protein, ?-glutamyl transferase and glucose. CONCLUSION:In conclusion, already at a young age heightened endogenous MBG levels may contribute to large artery stiffness in women via pressure-independent mechanisms, increasing their risk for future cardiovascular disease.

SUBMITTER: Strauss M

PROVIDER: S-EPMC6329631 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Large artery stiffness is associated with marinobufagenin in young adults: the African-PREDICT study.

Strauss Michél M Smith Wayne W Wei Wen W Bagrov Alexei Y AY Fedorova Olga V OV Schutte Aletta E AE

Journal of hypertension 20181201 12

<h4>Objectives</h4>The cardiotonic steroid, marinobufagenin (MBG), has been shown to play a physiological natriuretic role in response to salt intake. However, recent studies in clinical and animal models demonstrated possible links between elevated levels of endogenous MBG and increased arterial stiffness. Large artery stiffness is a known predictor of future cardiovascular disease. We, therefore, investigated whether large artery stiffness relates to 24-h urinary MBG excretion in young apparen ...[more]

PMID: 30382957

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Project description:Background The endogenous steroidal inhibitor of sodium-potassium-dependent adenosine triphosphate and natriuretic hormone, marinobufagenin, plays a physiological role in ionic homeostasis. Animal models suggest that elevated marinobufagenin adversely associates with cardiac and renal, structural and functional alterations. It remains uncertain whether marinobufagenin relates to the early stages of target organ damage development, especially in young adults without cardiovascular disease. We therefore explored whether elevated 24-hour urinary marinobufagenin excretion was related to indices of subclinical target organ damage in young healthy adults. Design This cross-sectional study included 711 participants from the African-PREDICT study (black 51%, men 42%, 24.8 ± 3.02 years). Methods We assessed cardiac geometry and function by two-dimensional echocardiography and pulse wave Doppler imaging. 24-Hour urinary marinobufagenin and sodium excretion were measured, and the estimated glomerular filtration rate determined. Results Across marinobufagenin excretion quartiles, left ventricular mass ( P < 0.001), end diastolic volume ( P < 0.001), stroke volume ( P = 0.004) and sodium excretion ( P < 0.001) were higher within the fourth compared with the first quartile. Partial regression analyses indicated that left ventricular mass ( r = 0.08, P = 0.043), end diastolic volume ( r = 0.10, P = 0.010) and stroke volume ( r = 0.09, P = 0.022) were positively related to marinobufagenin excretion. In multivariate-adjusted regression analysis, left ventricular mass associated positively with marinobufagenin excretion only in the highest marinobufagenin excretion quartile (adjusted R2 = 0.20; β = 0.15; P = 0.043). This relationship between left ventricular mass and marinobufagenin excretion was evident in women (adjusted R2 = 0.06; β = 0.127; P = 0.015) but not in men (adjusted R2 = 0.06; β = 0.007; P = 0.92). Conclusions Left ventricular mass positively and independently associates with marinobufagenin excretion in young healthy adults with excessively high marinobufagenin excretion. Women may be more sensitive to the effects of marinobufagenin on early structural cardiac changes.

Project description:IntroductionIncreased exposure to risk factors in the young and healthy contributes to arterial changes, which may be accompanied by an altered metabolism.ObjectivesTo increase our understanding of early metabolic alterations and how they associate with markers of arterial stiffness, we profiled urinary metabolites in young adults with cardiovascular disease (CVD) risk factor(s) and in a control group without CVD risk factors.MethodsWe included healthy black and white women and men (N = 1202), aged 20-30 years with a detailed CVD risk factor profile, reflecting obesity, physical inactivity, smoking, excessive alcohol intake, masked hypertension, hyperglycemia, dyslipidemia and low socio-economic status, forming the CVD risk group (N = 1036) and the control group (N = 166). Markers of arterial stiffness, central systolic blood pressure (BP) and pulse wave velocity were measured. A targeted metabolomics approach was followed by measuring amino acids and acylcarnitines using a liquid chromatography-tandem mass spectrometry method.ResultsIn the CVD risk group, central systolic BP (adjusted for age, sex, ethnicity) was negatively associated with histidine, arginine, asparagine, serine, glutamine, dimethylglycine, threonine, GABA, proline, methionine, pyroglutamic acid, aspartic acid, glutamic acid, branched chain amino acids (BCAAs) and butyrylcarnitine (all P ≤ 0.048). In the same group, pulse wave velocity (adjusted for age, sex, ethnicity, mean arterial pressure) was negatively associated with histidine, lysine, threonine, 2-aminoadipic acid, BCAAs and aromatic amino acids (AAAs) (all P ≤ 0.044). In the control group, central systolic BP was negatively associated with pyroglutamic acid, glutamic acid and dodecanoylcarnitine (all P ≤ 0.033).ConclusionIn a group with increased CVD risk, markers of arterial stiffness were negatively associated with metabolites related to AAA and BCAA as well as energy metabolism and oxidative stress. Our findings may suggest that metabolic adaptations may be at play in response to increased CVD risk to maintain cardiovascular integrity.

Project description:ObjectivesPhysical activity is negatively associated with arterial stiffness. However, the relationship between sedentary behaviour and arterial stiffness is poorly understood. In this study, we aimed to investigate the association of sedentary behaviour with arterial stiffness among young adults.DesignCross-sectional.Setting34 study clinics across Australia during 2004-2006.Participants2328 participants (49.4% male) aged 26-36 years who were followed up from a nationally representative sample of Australian schoolchildren in 1985.MeasurementsArterial stiffness was measured by carotid ultrasound. Sitting time per weekday and weekend day, and physical activity were self-reported by questionnaire. Cardiorespiratory fitness was estimated as physical work capacity at a heart rate of 170 bpm. Anthropometry, blood pressure, resting heart rate and blood biochemistry were measured. Potential confounders, including strength training, education, smoking, diet, alcohol consumption and parity, were self-reported. Rank correlation was used for analysis.ResultsSitting time per weekend day, but not per weekday, was correlated with arterial stiffness (males r=0.11 p<0.01, females r=0.08, p<0.05) and cardiorespiratory fitness (males r?=?-0.14, females r?=?-0.08, p<0.05), and also with fatness and resting heart rate. One additional hour of sitting per weekend day was associated with 5.6% (males p=0.046) and 8.6% (females p=0.05) higher risk of having metabolic syndrome. These associations were independent of physical activity and other potential confounders. The association of sitting time per weekend day with arterial stiffness was not mediated by resting heart rate, fatness or metabolic syndrome.ConclusionsOur study demonstrates a positive association of sitting time with arterial stiffness. The greater role of sitting time per weekend day in prediction of arterial stiffness and cardiometabolic risk than that of sitting time per weekday may be due to better reflection of discretionary sitting behaviour.

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Large artery stiffness is associated with marinobufagenin in young adults: the African-PREDICT study.

Publications

Large artery stiffness is associated with marinobufagenin in young adults: the African-PREDICT study.

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