A machine learning approach to personalized predictors of dyslipidemia: a cohort study

IntroductionMexico ranks second in the global prevalence of obesity in the adult population, which increases the probability of developing dyslipidemia. Dyslipidemia is closely related to cardiovascular diseases, which are the leading cause of death in the country. Therefore, developing tools that facilitate the prediction of dyslipidemias is essential for prevention and early treatment.MethodsIn this study, we utilized a dataset from a Mexico City cohort consisting of 2,621 participants, men and women aged between 20 and 50 years, with and without some type of dyslipidemia. Our primary objective was to identify potential factors associated with different types of dyslipidemia in both men and women. Machine learning algorithms were employed to achieve this goal. To facilitate feature selection, we applied the Variable Importance Measures (VIM) of Random Forest (RF), XGBoost, and Gradient Boosting Machine (GBM). Additionally, to address class imbalance, we employed Synthetic Minority Over-sampling Technique (SMOTE) for dataset resampling. The dataset encompassed anthropometric measurements, biochemical tests, dietary intake, family health history, and other health parameters, including smoking habits, alcohol consumption, quality of sleep, and physical activity.ResultsOur results revealed that the VIM algorithm of RF yielded the most optimal subset of attributes, closely followed by GBM, achieving a balanced accuracy of up to 80%. The selection of the best subset of attributes was based on the comparative performance of classifiers, evaluated through balanced accuracy, sensitivity, and specificity metrics.DiscussionThe top five features contributing to an increased risk of various types of dyslipidemia were identified through the machine learning technique. These features include body mass index, elevated uric acid levels, age, sleep disorders, and anxiety. The findings of this study shed light on significant factors that play a role in dyslipidemia development, aiding in the early identification, prevention, and treatment of this condition

Nutrient Patterns are Associated with Discordant Apolipoprotein B and Low-Density Lipoproteins: A Population-Based Analysis

Individuals with discordantly high ApoB to LDL-C levels carry a higher risk of atherosclerotic cardiovascular disease compared to those with average or discordantly low ApoB to LDL-C. We aimed to determine associations between ApoB and LDL-C discordance in relation to nutrient patterns (NPs) using National Health and Nutrition Examination Survey data. Participants were grouped by established LDL-C and ApoB cut-offs (Group 1: Low ApoB/Low LDL-C, Group 2: Low ApoB/High LDL-C, Group 3: High ApoB/Low LDL-C, Group 4: High ApoB/High LDL-C). Principle component analysis was used to define NPs. Machine learning (ML) and structural equation models were applied to assess associations of nutrient intake with ApoB/LDL-C discordance using the combined effects of ApoB and LDL-C. Three NPs explained 63.2% of variance in nutrient consumption. These consisted of NP1 rich in saturated fatty acids, carbohydrate and vitamins, NP2 high in fibre, minerals, vitamins and PUFA and NP3 rich in dietary cholesterol, protein, and sodium. The discordantly high ApoB to LDL-C group had the highest consumption of the NP1 and the lowest consumption of the NP2. ML showed nutrients which had the greatest unfavourable dietary contribution to individuals with discordantly high ApoB to LDL-C were total fat, saturated fatty acids and thiamine and the greatest favourable contributions were MUFA, folate, fibre and selenium. Individuals with discordantly high ApoB in relation to LDL-C had greater adherence to NP1, whereas those with lower levels of ApoB, irrespective of LDL-C, are more likely to consume NP3

Characterization of Vascular Disease Risk in Postmenopausal Women and Its Association with Cognitive Performance

Objectives: While global measures of cardiovascular (CV) risk are used to guide prevention and treatment decisions, these estimates fail to account for the considerable interindividual variability in pre-clinical risk status. This study investigated heterogeneity in CV risk factor profiles and its association with demographic, genetic, and cognitive variables. Methods: A latent profile analysis was applied to data from 727 recently postmenopausal women enrolled in the Kronos Early Estrogen Prevention Study (KEEPS). Women were cognitively healthy, within three years of their last menstrual period, and free of current or past CV disease. Education level, apolipoprotein E ε4 allele (APOE4), ethnicity, and age were modeled as predictors of latent class membership. The association between class membership, characterizing CV risk profiles, and performance on five cognitive factors was examined. A supervised random forest algorithm with a 10-fold cross-validation estimator was used to test accuracy of CV risk classification. Results: The best-fitting model generated two distinct phenotypic classes of CV risk 62% of women were “low-risk” and 38% “high-risk”. Women classified as low-risk outperformed high-risk women on language and mental flexibility tasks (p = 0.008) and a global measure of cognition (p = 0.029). Women with a college degree or above were more likely to be in the low-risk class (OR = 1.595, p = 0.044). Older age and a Hispanic ethnicity increased the probability of being at high-risk (OR = 1.140, p = 0.002; OR = 2.622, p = 0.012; respectively). The prevalence rate of APOE-ε4 was higher in the high-risk class compared with rates in the low-risk class. Conclusion: Among recently menopausal women, significant heterogeneity in CV risk is associated with education level, age, ethnicity, and genetic indicators. The model-based latent classes were also associated with cognitive function. These differences may point to phenotypes for CV disease risk. Evaluating the evolution of phenotypes could in turn clarify preclinical disease, and screening and preventive strategies

Pregnancy following bariatric surgery: maternal considerations

Background The mechanism behind the perinatal complications associated with obesity in pregnancy is not fully understood. There is convincing evidence that pregnancies following bariatric surgery have a lower incidence of gestational diabetes (GDM), pre-eclampsia (PE), large for gestational age (LGA) neonates, higher incidence of small for gestational age (SGA) neonates and moderately preterm birth. The mechanism for this is also unknown, however, could be related to changes in maternal insulin resistance and other metabolic pathways involved in glucose and fat metabolism. Aims 1. To investigate the effects of bariatric surgery on maternal insulin resistance, waist to hip ratio (WHR), blood pressure and components of fat and glucose metabolism such as adipokines, pro-inflammatory hormones, incretins and metabolites. 2. To compare the lipoprotein profile of obese women and women with a normal BMI in the third trimester, without previous bariatric surgery. Method We conducted a prospective, longitudinal study comparing pregnant women with previous bariatric surgery to those without surgery. The following were assessed: 1. Insulin, glucose, glycosylated haemoglobin (HbA1c), Homeostasis Model Assessment of insulin resistance (HOMA-IR) and the Matsuda Index were measured using fasting blood samples collected at 28 weeks gestation. 2. Maternal weight, height, waist to hip ratio (WHR) and blood pressure were measured at all antenatal visits. 3. Fasting blood samples at 28+0-30+0 weeks’ gestation were used to measure peptide hormones, adipokines, pro-inflammatory hormones and incretins. 4. Untargeted metabolomics with proton Nuclear Magnetic Resonance (H1 NMR) was performed on samples obtained at six time points: 11+0-14+0 (T1), 20+0-24+0 (T2), 28+0-30+0 (T3), 30+0-33+0 (T4) and 35+0-37+6 (T5) weeks’ gestation, and within 72 hours of delivery (T6). H1 NMR lipoprotein profiling was performed for pregnant women recruited without previous bariatric surgery at 28+0-30+0 weeks’ gestation. Results were compared between women with normal BMI and women who were obese (BMI ≥ 30kg/m2). Results The no surgery group had higher median insulin resistance (IR), [2.20 (IQR 1.53-3.38)] compared to the post bariatric surgery group [1.15 (IQR 1.04 -2.07); p <0.05] and post malabsorptive bariatric surgery group, [1.08 (0.99 – 1.23; p <0.05]. Pregnant women with previous bariatric surgery had significantly lower leptin levels at 28-30 weeks [13.3ng/ml (IQR 9.71-15.36)] compared to women with no surgery [20.84ng/ml (IQR 18.12-24.1); p<0.05]. Maternal adiponectin levels at 28-30 weeks of gestation were higher in the post bariatric women [4.9µg/ml (IQR 2.9-6.7)] compared to no surgery women [2.43 µg/ml (IQR 1.8-3.2); p <0.05]. Pregnant women with previous malabsorptive bariatric surgery had an altered serum metabolome by T4 (30-33 weeks) and T5 (35-37 weeks) compared to those without bariatric surgery (p=0.027 and p=0.006, respectively). There is a lower serum level of unsaturated lipids, isobutyrate, leucine, isoleucine and N-acetyl glycoprotein and higher level of glutamine and D-ß-hydroxybutyrate. The lipoprotein profile of women at 28 weeks gestation without surgery showed that, compared to women with normal BMI, obese women have higher levels of HDL4 Triglyceride (p=0.02) VLDL1 Phospholipid (p=0.023) and VLDL1 Cholesterol (p=0.02) and lower levels of HDL, HDL1 cholesterol (p=0.02, 0.02), LDL2, LDL3 cholesterol (p=0.03, 0.02) and HDL1 phospholipid (p=0.03). Conclusion The study has demonstrated that women with previous bariatric surgery have a reduction in insulin resistance, especially post malabsorptive surgery. In the third trimester, they have a lower leptin and higher adiponectin level. These findings may explain the reduced incidence of GDM and LGA babies seen in this group.Open Acces

Nutrient patterns are associated with discordant apoB and LDL: a population-based analysis

Individuals with discordantly high apoB to LDL-cholesterol levels carry a higher risk of atherosclerotic CVD compared with those with average or discordantly low apoB to LDL-cholesterol. We aimed to determine associations between apoB and LDL-cholesterol discordance in relation to nutrient patterns (NP) using National Health and Nutrition Examination Survey data. Participants were grouped by established LDL-cholesterol and apoB cut-offs (Group 1: low apoB/low LDL-cholesterol, Group 2: low apoB/high LDL-cholesterol, Group 3: high apoB/low LDL-cholesterol, Group 4: high apoB/high LDL-cholesterol). Principle component analysis was used to define NP. Machine learning (ML) and structural equation models were applied to assess associations of nutrient intake with apoB/LDL-cholesterol discordance using the combined effects of apoB and LDL-cholesterol. Three NP explained 63·2 % of variance in nutrient consumption. These consisted of NP1 rich in SFA, carbohydrate and vitamins, NP2 high in fibre, minerals, vitamins and PUFA and NP3 rich in dietary cholesterol, protein and Na. The discordantly high apoB to LDL-cholesterol group had the highest consumption of the NP1 and the lowest consumption of the NP2. ML showed nutrients that had the greatest unfavourable dietary contribution to individuals with discordantly high apoB to LDL-cholesterol were total fat, SFA and thiamine and the greatest favourable contributions were MUFA, folate, fibre and Se. Individuals with discordantly high apoB in relation to LDL-cholesterol had greater adherence to NP1, whereas those with lower levels of apoB, irrespective of LDL-cholesterol, were more likely to consume NP3

Human body composition: measurement and relationship with exercise, dietary intakes and cardiovascular risk factors

This thesis describes studies related to human body composition, concentrating upon methodology of measurement, and a study on the influence of brisk walking programme upon healthy, previously sedentary middle-aged men. In chapter I, the principles of the techniques used for measurement of body composition in this thesis are discussed. The limitations and potential sources of error associated with each are discussed. The response of body composition to exercise, and the relationship of this response to changes in cardiovascular risk factors are considered. General methods are described in chapter 2. Techniques suitable for measurement of body composition in "field" conditions are evaluated in chapters 3 and 4. Near infra-red interactance was found to under-estimate fatness, to an increasing extent with increasing fatness. Bio-electrical impedance estimates of body composition from different sets of prediction equations from the literature differed significantly. Most overestimated fatness, to an increasing extent with increasing fatness. In chapter 5 techniques for measurement of subcutaneous adipose tissue are evaluated by comparison with A-mode ultrasound. Skinfold thicknesses were better correlated with subcutaneous adipose tissue thickness than were interactance data. Chapters 6 and 7 describe a year-long study on the effects of a brisk walking programme on healthy, previously sedentary middle-aged men. Volunteers were randomly allocated to walking or control groups (n = 42 and 23 respectively). Brisk walking for on average 27 minutes per day was not found to influence body composition, although significant changes in lower limb skinfold thicknesses were observed. The relationship of changes in blood pressure and blood concentrations of total cholesterol, lipoprotein-cholesterol subfractions and triglycerides with changes in body composition and fat distribution is examined. Energy intake did not change during the study, despite the expected increase in energy expenditure, and lack of change in body composition. Changes in dietary cholesterol and fatty acid intakes during the year are described, and related to changes in cardiovascular risk factors. In conclusion, newer field techniques were not found to be a better predictor of body composition than skinfold thicknesses. Participation in the walking programme did not significantly influence body composition or energy intake

Aerospace Medicine and Biology: A continuing bibliography with indexes, supplement 140

This bibliography lists 306 reports, articles, and other documents introduced into the NASA scientific and technical information system in March 1975

The potential association between thiamin, hyperglycemia and chronic diseases

Chronic diseases, such as cardiovascular disease and diabetes, are the leading causes of morbidity and mortality worldwide. Recent studies have shown that in addition to diabetes mellitus, non-diabetic degrees of fasting and postprandial hyperglycemia are also directly linked to accelerated risks of cardiovascular diseases. Thiamin is a water soluble vitamin playing a key regulatory role as a co-enzyme in metabolic pathways implicated in the glucose metabolism. There is some evidence that diabetic patients are prone to thiamin deficiency possibly because of an increased excretion of thiamin in the urine. However, there has been no published study to investigate thiamin status in individuals with pre-diabetic range of hyperglycemia. Given this gap, we undertook a cross-sectional study, evaluating blood thiamin concentration of subjects with impaired glucose regulation compared with healthy people.To examine the main objective of this study, data of 64 subjects (29 men and 35 women) were analysed. These subjects consisted of 39 normal healthy volunteers and 25 hyperglycemics with plasma glucose levels at pre-diabetic ranges (16 IGT, 9 IFG). The mean intake of thiamin in both groups as assessed by a validated semiquantitative food frequency questionnaire was 1.37±0.72 mg/day for normal subjects and 1.46±0.51 mg/day for those with hyperglycemia. These values exceeded the Australian RDI for thiamin. There was no significant difference in the levels of RBC thiamin in hyperglycemic subjects relative to those in the normoglycemic group (0.95±0.17 vs. 0.88±0.24 nmol/g Hb, p=0.22).The two groups were also evaluated for a range of risk factors for CVD, including arterial stiffness. Hyperglycemic subjects had higher levels of fasting DVP parameters (SI & RI), accompanied with tendencies toward blunted response to ingested glucose load relative to normoglycemic group. These results suggest that screening of individuals with hyperglycemia by using a Pulse Trace machine may be a means of recognising cardiovascular complications at early stages. Further research with a larger sample size is recommended to extend these interesting results.Hyperglycemia is known to induce a variety of biochemical alterations at the cellular level, resulting in a range of vascular and tissue damages. The mechanism of action of supplemental thiamin seems to involve the diversion of "excess" metabolic load (glycolytic intermediates) away from glycolysis and toward the reductive pentose pathway, a secondary pathway for glucose catabolism. Thiamin supplementation was also shown to improve cardiovascular risk factors in diabetic rats, suggesting the potential effects of thiamin in prevention of diabetic complications.To date there has been no published study to investigate these effects in individuals with pre-diabetic range of hyperglycemia (IGT). Therefore, our objective in the second study was to assess the chronic effect of high dose thiamin supplement (300 mg/d) on glucose tolerance and some cardiovascular risk factors in individuals with hyperglycemia at an early stage. In this intervention study with a double blind cross - over design, the hyperglycemic subjects (n=12) were randomly allocated into two groups to receive either placebo for 6 weeks followed by a 14-week washout period and then thiamin for 6 weeks; or thiamin for 6 weeks, a 14-week washout period and placebo for 6 weeks.The results of our intervention study showed that after 6 weeks of supplementation, RBC thiamin increased from 0.93 (±0.17) nmol/g Hb to 1.56 (±0.31) nmol/g Hb. In subjects receiving placebo, fasting plasma glucose increased significantly from baseline after six weeks (6.11±0.70 vs. 5.87±0.63 mmol/L, p=0.003). This significant change was accompanied with concomitant increases in fasting plasma insulin (7.67± 4.39 vs. 6.64± 3.45 μIU/mL, p=0.04), and HOMA score (2.10±1.32 vs. 1.75±1.01, p= 0.02). However in the supplement arm, there was no significant change in fasting plasma glucose (6.01±0.79 vs. 6.02±0.68 mmol/L, p=0.83), fasting insulin (7.46 ±4.67 vs. 7.36± 4.40 μIU/mL, p> 0.05) or HOMA score (2.05±1.51 vs. 2.00±1.32, p=0.75) determined at week 6 compared to baseline (week 0), indicating that supplementation with high dose thiamin may have prevented the natural progression of hyperglycemia toward diabetes mellitus in individuals with impaired glucose metabolism at early stages. We also found that high dose thiamin therapy can improve glucose tolerance (week 0: 9.89±2.50 vs. week 6: 8.78±2.20 mmol/L, p=0.004), and attenuate diastolic blood pressure (week 0: 71.42 ±7.41 vs. week 6: 79.2± 5.84 mm Hg, p=0.005) in patients with impaired glucose metabolism. The findings of the present study suggest that thiamin therapy may be effective in patients with hyperglycemia at early stages.Previous studies examining the potential effects of thiamin under hyperglycemic condition have mainly been limited to animals. The current clinical study suggests that thiamin supplementation may be beneficial in humans with pre-diabetic ranges of hyperglycemia. Further studies are required to confirm these results and investigate the impact of thiamin supplementation on insulin secretion.The findings of this research have the potential to inform food formulations and dietary recommendations for people who are at risk of developing diabetes mellitus, and may have a role in the prevention of hyperglycemic complications. The findings of this study serve as a base for further research investigating the effectiveness of different doses of thiamin on cardiovascular risk factors

Predictors and methological issues in tracking total body fat mass, trunk fat, mass and abdominal fat mass : changes in a weight loss intervention with overweight and obese women.

Doutoramento em Motricidade Humana, especialidade de Saúde e Condição FísicaOne of the purposes of this dissertation was to analyze the usefulness of simple anthropometric measurements in predicting total body fat mass, as well as trunk and abdominal fat regions of interest, assessed by DXA, along with their changes in a weight loss program. Another purpose was to examine the influence of different physical activity dimensions on body weight, total body fat mass, abdominal and trunk fat regions of interest, selected by conventional whole body DXA in premenopausal overweight and obese women. Three studies were conducted within the PESO Program (Promotion of Exercise and Health in Obesity), a behavioural intervention addressed to premenopausal overweight and obese women. Key results show that: a) changes in lifestyle habits during a weight loss intervention may provide a stimulus to reduce trunk fat mass, with special focus on abdominal fat mass; b) abdominal circumference is a better predictor of body fat mass loss than waist circumference; c) baseline values of body weight, BMI, sagital diameter and hip circumference, are able to predict total body fat mass changes, but are unable to predict alterations in more specific depots of body fat estimated by DXA; d) alterations in DXA abdominal fat mass estimations were reasonably detected by all the anthropometric variables, but cannot be used to quantify fat mass loss; e) physical activity variables did not induce changes in total body fat mass and body weight; f) an increase in the total amount of physical activity and the increment of total minutes walking played an important role in the reduction of abdominal fat mass estimated by DXA in obese women. RESUMO: Analisar a utilidade de simples medidas antropométricas na predição da massa gorda corporal total, assim como da massa gorda do tronco e região abdominal, estimadas por uma região de interesse obtida pela DXA, bem como as suas alterações, foi um dos objectivos desta dissertação. Outro dos objectivos desta tese prendeu-se com a análise da influência de diferentes dimensões de actividade física no peso corporal, massa gorda corporal total e regiões de interesse (tronco e abdominal) estimadas pela DXA em mulheres com excesso de peso ou obesas. Três estudos foram realizados com base no Programa PESO (Promoção do Exercício e da Saúde na Obesidade), uma intervenção de modificação comportamental em mulheres com excesso de peso ou obesas. Os resultados destes estudos demonstraram que: a) as alterações no estilo de vida durante uma intervenção de perda de peso podem constituir um estímulo na redução da massa gorda do tronco, em particular da massa gorda abdominal; b) o perímetro abdominal prediz melhor a perda de massa gorda corporal total do que o perímetro da cintura; c) os valores iniciais do peso corporal, IMC, diâmetro sagital e perímetro da anca, são bons predictores das alterações da massa gorda corporal total, mas são ineficazes na predição das alterações dos depósitos mais específicos estimados pela DXA; d) as alterações na estimação da massa gorda abdominal obtida pela DXA foram razoavelmente detectadas por todas as medidas antropométricas, mas estas medidas não podem ser utilizadas na quantificação da perda de massa gorda; e) as variáveis de actividade física não induziram alterações na massa gorda corporal total e no peso corporal; f) um incremento na quantidade total de actividade física e um incremento no número de minutos a caminhar podem ter um papel importante na redução da massa gorda abdominal estimada pela DXA em mulheres obesas