scholarly journals Sex differences in systemic metabolites at four life stages: cohort study with repeated metabolomics

BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Joshua A. Bell ◽  
Diana L. Santos Ferreira ◽  
Abigail Fraser ◽  
Ana Luiza G. Soares ◽  
Laura D. Howe ◽  
...  
Keyword(s):  
Sex Differences ◽  
Ldl Cholesterol ◽  
Proton Nuclear Magnetic Resonance ◽  
Low Density ◽  
Life Stages ◽  
Middle Adulthood ◽  
Linear Regression Models ◽  
Lipoprotein Subclass ◽  
Very Low Density Lipoproteins ◽  
Opposite Pattern

Abstract Background Males experience higher rates of coronary heart disease (CHD) than females, but the circulating traits underpinning this difference are poorly understood. We examined sex differences in systemic metabolites measured at four life stages, spanning childhood to middle adulthood. Methods Data were from the Avon Longitudinal Study of Parents and Children (7727 offspring, 49% male; and 6500 parents, 29% male). Proton nuclear magnetic resonance (1H-NMR) spectroscopy from a targeted metabolomics platform was performed on EDTA-plasma or serum samples to quantify 229 systemic metabolites (including lipoprotein-subclass-specific lipids, pre-glycaemic factors, and inflammatory glycoprotein acetyls). Metabolites were measured in the same offspring once in childhood (mean age 8 years), twice in adolescence (16 years and 18 years) and once in early adulthood (25 years), and in their parents once in middle adulthood (50 years). Linear regression models estimated differences in metabolites for males versus females on each occasion (serial cross-sectional associations). Results At 8 years, total lipids in very-low-density lipoproteins (VLDL) were lower in males; levels were higher in males at 16 years and higher still by 18 years and 50 years (among parents) for medium-or-larger subclasses. Larger sex differences at older ages were most pronounced for VLDL triglycerides—males had 0.19 standard deviations (SD) (95% CI = 0.12, 0.26) higher at 18 years, 0.50 SD (95% CI = 0.42, 0.57) higher at 25 years, and 0.62 SD (95% CI = 0.55, 0.68) higher at 50 years. Low-density lipoprotein (LDL) cholesterol, apolipoprotein-B, and glycoprotein acetyls were generally lower in males across ages. The direction and magnitude of effects were largely unchanged when adjusting for body mass index measured at the time of metabolite assessment on each occasion. Conclusions Our results suggest that males begin to have higher VLDL triglyceride levels in adolescence, with larger sex differences at older ages. Sex differences in other CHD-relevant metabolites, including LDL cholesterol, show the opposite pattern with age, with higher levels among females. Such life course trends may inform causal analyses with clinical endpoints in specifying traits which underpin higher age-adjusted CHD rates commonly seen among males.

scholarly journals Sex differences in cardiometabolic traits at four life stages: cohort study with repeated metabolomics

2020 ◽  
Author(s):  
Joshua A. Bell ◽  
Diana L. Santos Ferreira ◽  
Abigail Fraser ◽  
Ana Luiza G. Soares ◽  
Laura D. Howe ◽  
...  
Keyword(s):  
Amino Acids ◽  
Sex Differences ◽  
Cohort Study ◽  
Sex Difference ◽  
Apolipoprotein B ◽  
Low Density Lipoproteins ◽  
Low Density ◽  
Life Stages ◽  
Middle Adulthood ◽  
Cardiometabolic Traits

AbstractBackgroundMales experience higher rates of coronary heart disease (CHD) than females, but the circulating traits underpinning this difference are poorly understood. We examined sex differences in detailed cardiometabolic traits measured at four life stages, spanning childhood to middle adulthood.Methods and ResultsData were from the Avon Longitudinal Study of Parents and Children cohort study. 229 traits quantified from targeted metabolomics (nuclear magnetic resonance spectroscopy) including lipoprotein subclass-specific cholesterol and triglycerides, amino acids, glucose, and inflammatory glycoprotein acetyls were measured repeatedly in offspring (Generation 1 (G1)) born in 1991-92 and once in their parents (Generation 0 (G0)). Measurements in G1 were once in childhood (mean age 8y), twice in adolescence (16y and 18y) and once in early adulthood (25y), and in G0 once in middle adulthood (50y). Linear regression models were used to examine differences in standardized traits for males compared with females on each occasion (serial cross-sectional associations). 7,727 G1s (49% male) and 6,500 G0s (29% male) contributed to analyses. At age 8y, total lipids in very-low-density lipoproteins (VLDL) were lower in males than females; levels were higher in males than females at age 16y and were higher still by age 18y and age 50y (in G0) for medium-or-larger subclasses. Larger sex differences at older ages were most pronounced for triglycerides in VLDL – e.g. male levels were 0.19 standard deviation (SD) units (95% CI=0.12, 0.26) higher at age 18y, 0.50 SD (95% CI=0.42, 0.57) higher at age 25y, and 0.62 SD (95% CI=0.55, 0.68) higher at age 50y. Cholesterol in VLDL and low-density lipoproteins (LDL) was generally lower in males, with inconsistent sex differences across ages. Apolipoprotein-B was generally lower in males than females. Branched chain amino acids were consistently higher in males after age 8y with the largest sex difference of all traits at all ages seen for leucine at age 50y (1.53 SD, 95% CI=1.47, 1.58 higher in males compared with females). Males had consistently lower glycoprotein acetyls across ages.ConclusionsOur results suggest that males begin to have higher VLDL triglycerides in adolescence, and that this sex difference is larger at older ages. Sex differences in other CHD-related traits, including LDL cholesterol, apolipoprotein-B, and inflammatory glycoproteins, show the opposite pattern with age, with higher levels among females. Higher triglyceride content may therefore be a key factor underpinning the higher age-adjusted rate of CHD among males; causal analyses of this and other traits are needed to understand whether they differentially affect CHD risk among males and females.

Triglyceride Management in Cardiovascular Risk Reduction

2005 ◽  
Vol 00 (01) ◽  
pp. 31
Author(s):  
Michael Miller
Keyword(s):  
Metabolic Syndrome ◽  
Risk Factor ◽  
Cardiovascular Risk ◽  
Ldl Cholesterol ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Low Density ◽  
Very Low Density Lipoproteins ◽  
The Metabolic Syndrome ◽  
Ldl Particles

Elevated triglycerides are now considered an independent risk factor for coronary heart disease (CHD), even apart from elevated low-density lipoprotein (LDL) cholesterol. While the primary lipid target for CHD risk management remains LDL cholesterol, the treatment of elevated triglycerides is now also recommended. Elevated triglycerides are believed to increase cardiovascular risk because certain triglyceride-rich lipoproteins, called remnant lipoproteins (partially degraded chylomicrons and very-low density lipoproteins (VLDL)), are atherogenic. Hypertri-glyceridemia, together with low levels of high-density lipoprotein (HDL) cholesterol and an increased prevalence of small, dense LDL particles, comprise a triad of lipid risk factors known as atherogenic dyslipidemia.The significance of hypertriglyceridemia as a cardiovascular risk factor is further highlighted by its inclusion as a component of the metabolic syndrome, a cluster of metabolic abnormalities, related to insulin resistance. The other criteria for metabolic syndrome include low HDL cholesterol, central obesity, elevated blood pressure, and abnormal fasting glucose. The metabolic syndrome is recognized as a major risk factor not only for premature CHD but also for type 2 diabetes mellitus.

scholarly journals Cardiometabolic Associations between Physical Activity, Adiposity, and Lipoprotein Subclasses in Prepubertal Norwegian Children

Nutrients ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 2095
Author(s):  
Tarja Rajalahti ◽  
Eivind Aadland ◽  
Geir Kåre Resaland ◽  
Sigmund Alfred Anderssen ◽  
Olav Martin Kvalheim
Keyword(s):  
Physical Activity ◽  
Density Lipoprotein ◽  
Principal Component ◽  
Proton Nuclear Magnetic Resonance ◽  
High Density Lipoproteins ◽  
Resonance Spectroscopy ◽  
Low Density ◽  
Very Low Density Lipoproteins ◽  
Lipoprotein Subclasses ◽  
Ldl Particles

Lipoprotein subclasses possess crucial cardiometabolic information. Due to strong multicollinearity among variables, little is known about the strength of influence of physical activity (PA) and adiposity upon this cardiometabolic pattern. Using a novel approach to adjust for covariates, we aimed at determining the “net” patterns and strength for PA and adiposity to the lipoprotein profile. Principal component and multivariate pattern analysis were used for the analysis of 841 prepubertal children characterized by 26 lipoprotein features determined by proton nuclear magnetic resonance spectroscopy, a high-resolution PA descriptor derived from accelerometry, and three adiposity measures: body mass index, waist circumference to height, and skinfold thickness. Our approach focuses on revealing and validating the underlying predictive association patterns in the metabolic, anthropologic, and PA data to acknowledge the inherent multicollinear nature of such data. PA associates to a favorable cardiometabolic pattern of increased high-density lipoproteins (HDL), very large and large HDL particles, and large size of HDL particles, and decreasedtriglyceride, chylomicrons, very low-density lipoproteins (VLDL), and their subclasses, and to low size of VLDL particles. Although weakened in strength, this pattern resists adjustment for adiposity. Adiposity is inversely associated to this pattern and exhibits unfavorable associations to low-density lipoprotein (LDL) features, including atherogenic small and very small LDL particles. The observed associations are still strong after adjustment for PA. Thus, lipoproteins explain 26.0% in adiposity after adjustment for PA compared to 2.3% in PA after adjustment for adiposity.

Platelet Aggregation and Plasma Lipoproteins in Alcoholics During Alcohol Withdrawal

1986 ◽  
Vol 55 (02) ◽  
pp. 173-177 ◽  
Author(s):  
K Desai ◽  
J S Owen ◽  
D T Wilson ◽  
R A Hutton
Keyword(s):  
Platelet Aggregation ◽  
Alcohol Withdrawal ◽  
Ldl Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Plasma Lipoprotein ◽  
Cholesterol Concentration ◽  
Arachidonic Acid Content ◽  
Low Density

SummaryPlatelet aggregation, platelet lipid composition and plasma lipoprotein concentrations were measured each week in a group of seventeen alcoholics, without overt liver disease, for one month, following acute, total alcohol withdrawal. The platelets were initially hypoaggregable but, within 1-2 weeks of cessation of drinking, they became hyperaggregable and then gradually returned towards normal values. Hyperaggregability could not be explained by increases in either the cholesterol or the arachidonic acid content of the platelets. Plasma very-low-density lipoprotein cholesterol levels remained high throughout the study, but the initially raised levels of high-density lipoprotein (HDL) cholesterol fell by 26%. Low-density lipoprotein (LDL) cholesterol concentration rose by 10% after two weeks of withdrawal but then returned to about the starting level. The resulting changes in the plasma LDL-cholesterol: HDL-cholesterol ratio, which had increased by more than 50% after two weeks of abstinence, essentially paralleled the time course of enhanced platelet reactivity in all but four of the alcoholics. These findings suggest that alterations in plasma lipoprotein concentrations during acute alcohol withdrawal may be a contributory factor to the haemostatic disorders present in such patients.

scholarly journals Studies of the Proteins in Human Plasma Very Low Density Lipoproteins

1969 ◽  
Vol 244 (20) ◽  
pp. 5687-5694 ◽  
Author(s):  
W. Virgil Brown ◽  
Robert I. Levy ◽  
Donald S. Fredrickson
Keyword(s):  
Human Plasma ◽  
Low Density Lipoproteins ◽  
Low Density ◽  
Very Low Density Lipoproteins

scholarly journals Effects of Weight Gain after 20 Years of Age and Incidence of Hyper-Low-Density Lipoprotein Cholesterolemia: The Iki Epidemiological Study of Atherosclerosis and Chronic Kidney Disease (ISSA-CKD)

2021 ◽  
Vol 10 (14) ◽  
pp. 3098
Author(s):  
Shota Okutsu ◽  
Yoshifumi Kato ◽  
Shunsuke Funakoshi ◽  
Toshiki Maeda ◽  
Chikara Yoshimura ◽  
...  
Keyword(s):  
Weight Gain ◽  
General Population ◽  
Ldl Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Population Based ◽  
Lipid Lowering ◽  
Low Density ◽  
Obesity Hypertension ◽  
Old Men

The aim of this study was to investigate the effects of long-term weight gain from the age of 20 on incidence of hyper-low-density-lipoprotein (LDL) cholesterolemia in the general population of Japanese people. Methods: We conducted a population-based retrospective cohort study using annual health checkup data for residents of Iki City, Nagasaki Prefecture, Japan. A total of 3179 adult (≥30 years old) men and women without hyper-LDL cholesterolemia at baseline, who underwent two or more health checkups were included in the analysis. Information on weight gain (≥10 kg) after 20 years of age was obtained using questionnaire. The outcome of this study was development of hyper-LDL cholesterolemia defined as LDL-cholesterol level ≥3.62 mmol/L and/or initiation of lipid-lowering medications. Results: During a mean follow-up period of 4.53 years, 665 of the 3179 participants developed hyper-LDL cholesterolemia (46.5/1000 person-years). The incidence of hyper-LDL cholesterolemia was higher in participants with a weight gain of ≥10 kg (55.3/1000 person-years) than among those with a weight gain of <10 kg (41.8/1000 person-years). This association remained statistically significant even after adjustment for age, sex, smoking, daily drinking, exercise, obesity, hypertension, and diabetes (multivariable hazard ratio 1.31, 95% confidence interval 1.08–1.58, p = 0.006). Conclusion: A weight gain of ≥10 after 20 years of age affected the development of hyper-LDL cholesterol regardless of age, sex, and obesity in a general population of Japanese.

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