Cardiovascular risk factors in children

Non-communicable diseases, above all cardiovascular disease (CVD), are the most common causes of morbidity and mortality in Europe. CVD has been shown to have its roots in childhood, although the clinical manifestations do not become evident until several decades later. The adolescent CVD risk profile has been shown to predict the extent of the atherosclerotic process in adulthood, even if the nature of the effects of biological and lifestyle factors, and their interactions, on the CVD risk profile in children and adolescents are largely unknown. The same holds true for the secular trends. The overall purpose of the present research was to increase our knowledge of physical activity, fitness, blood pressure, blood lipids, insulin and glucose, and the interactions between them, in children aged 9 and 15 years. Data collection took place during the school year 1998/1999 in central Sweden, and the 1,137 subjects constitute the Swedish part of the European Youth Heart Study. The level and pattern of physical activity were objectively assessed with a uniaxial accelerometer, and cardiorespiratory fitness was estimated by a maximal ergometer bike test. Body composition was estimated from skinfold thicknesses, blood pressure was measured by an automatic oscillometric method, and fasting serum samples were analysed for insulin, glucose, triglycerides, total cholesterol and high density lipoprotein cholesterol. The main outcomes in this population sample of healthy school children were: insulin was particularly influenced by body fat and total physical activity; data suggest a secular trend towards decreased cardiorespiratory fitness in 9-year-olds, but not in 15-year-olds; and a high fitness level was more important than high total physical activity level for a favourable CVD risk profile, but a gender difference was observed. The practical implications of these findings are that fitness, and not only total physical activity, ought to be considered in longitudinal and future intervention studies, and that the gender perspective of these issues needs further attention

The importance of cardiorespiratory fitness and sleep duration in early CVD prevention: BMI, resting heart rate and questions about sleep patterns are suggested in risk assessment of young adults, 18–25 years : The cross-sectional lifestyle, biomarkers and atherosclerosis (LBA) study.

Background Cardiorespiratory fitness (CRF) and sleep habits are lifestyle factors with potential to prevent cardiovascular disease (CVD). CVD is the leading cause of death worldwide. It is therefore important to establish a healthy lifestyle at a young age. In the Lifestyle, Biomarkers and Atherosclerosis (LBA) study we have examined 834 healthy non-smoking adults, aged 18–25 years. The general purpose of the LBA study was to study the effect of lifestyle on traditional biomarkers known to influence CVD risk. The aims of the present study were to evaluate sleep habits of young adult women and men participating in the LBA study, and to compare the importance of sleep and other lifestyle habits on clinically relevant biomarkers for CVD. An additional aim was to find easy and reliable non-invasive biomarkers to detect young adults with increased risk of developing CVD later in life. Methods The participants had previously been examined for lifestyle factors, biomarkers and CVD risk score. They filled in a validated computerized questionnaire about their general physical and mental health. The questionnaire included questions on sleep duration and experienced quality of sleep. Results In total 27% of the young adult participants reported difficulties falling asleep or experienced troubled sleep with frequent awakenings per night. The experienced troubled sleep was not related to a higher CVD risk score, but sleep quality and duration were correlated. Shorter sleep duration was significantly associated to higher body mass index (BMI), body fat (%), homeostasis model assessment of insulin resistance (HOMA-IR) and CVD risk. The modifiable lifestyle factor with the highest odds ratio (OR) for CVD risk was CRF. Sleep duration was the second most influential lifestyle factor, more important than moderate- and vigorous physical activity (MVPA) and food habits. Correlations between CRF and heart rate (HR), (P < 0.01) and HOMA-IR and BMI (P < 0.01) were observed, indicating that BMI and resting HR in combination with questions about sleep patterns are easy and reliable non-invasive biomarkers to detect young adults who need counselling on a healthy lifestyle. Conclusion Decreased sleep duration in combination with decreased CRF, in young adults, is a serious health issue

Higher Total Physical Activity is Associated with Lower Arterial Stiffness in Swedish, Young Adults : The Cross-Sectional Lifestyle, Biomarkers, and Atherosclerosis Study

Purpose: Arterial stiffness describes the rigidity of the arterial walls and is associated withrisk factors for cardiovascular disease (CVD). Arterial stiffness predicts future events andmortality, and the predictive value is stronger in younger versus older subjects. The aims ofthe present study were, firstly, to present data on physical activity (PA) and time spentsedentary, in the population of Swedish, young adults. Secondly, to explore the associationbetween PA and arterial stiffness. Material and Methods: Self-reported healthy, non-smoking, Swedish, young adults, 18–25years old, participated in the cross-sectional Lifestyle, Biomarkers and Atherosclerosis(LBA) study. The daily PA was objectively measured with an accelerometer for 1 week.Of the 834 participants, 658 individuals had valid registrations. The arterial stiffness measures, pulse wave velocity (PWV) and augmentation index (AIx) were measured withapplanation tonometry. Results: Women were on overall more physically active than men, they spent 214 min/dayin light PA (LPA) compared to men who spent 202 min/day. Women took significantly moresteps per day than men, 7796 vs 7336 steps/day, and spent less time sedentary, 523 min/day,compared to men who spent 547 min/day sedentary. In total, 76% of the individuals spent onaverage at least 30 minutes per day in the recommended moderate and vigorous PA (MVPA).Lower arterial stiffness was associated with more MVPA and total PA in the total population. Conclusion: We conclude that in this age group of young, self-reported healthy adults18–25 years, it is important to highlight the health-enhancing possibilities of time spent inphysical activity on the vascular function, measured as PWV and AIx. It is of high relevancein a public health perspective to expand preventive efforts beyond the high-risk groups andencourage young adults to be physically active

CRP levels are significantly associated with CRP genotype and estrogen use in The Lifestyle, Biomarker and Atherosclerosis (LBA) study

Background: The C‑reactive protein (CRP) is an important biomarker for atherosclerosis and single nucleotide poly‑morphisms (SNPs) in the CRP locus have been associated with altered CRP levels and associated with risk for cardio‑vascular disease. However, the association between genetic variations in the CRP gene, estrogen use and CRP levels orearly signs of atherosclerosis in young healthy individuals is not fully characterized. We aimed to evaluate the influ‑ence of five genetic variants on both plasma CRP levels and carotid intima‑media thickness (cIMT) values, includingaspects on estrogen containing contraceptive use in females. Methods: Genotyping was performed with TaqMan real time PCR and compared with high sensitivity CRP serumlevels in 780 Swedish young, self‑reported healthy individuals. Haplotypes of the SNPs were estimated with the PHASEv 2.1. The cIMT was measured by 12 MHz ultrasound. The contraceptive use was self‑reported. Results: Strong associations between CRP and genotype were observed for rs3091244, rs1800947, rs1130864, andrs1205 in women (all p &lt; 0.001). In men, only rs1800947 was associated with CRP (p = 0.029). The independent effectof genotypes on CRP remained significant also after adjustment for established risk factors. Female carriers of the H1/ATGTG haplotype had higher CRP than non‑carriers. This was specifically pronounced in the estrogen‑using group(p &lt; 0.001), and they had also higher cIMT (p = 0.002) than non‑carriers but with a small cIMT difference between thehaplotype groups (0.02 mm). In parallel, a significant correlation between CRP and cIMT in the estrogen using groupwas observed (r = 0.194; p = 0.026). Conclusions: Estrogen use, genotypes and haplotypes in the CRP locus are significantly associated with CRP levels.Based on an observed interaction effect between sex/estrogen use and the H1/ATGTG haplotype on CRP, and amarginally thicker cIMT in the estrogen using group, our data suggest that both genotypes and estrogen usage couldbe involved in arterial wall structural differences. The causality between CRP levels and cIMT remains unclear, and theobserved difference in cIMT is not clinically relevant in the present state. Future larger and longitudinal studies mayshed further light on the role of more long‑term estrogen use and early atherosclerosis.Funding agency:Örebro University, Faculty of Medicine and Health 2019-06-13</p

Insulin resistance (HOMA-IR) and body fat (%) are associated to low intake of fruit and vegetables in Swedish, young adults: the cross-sectional lifestyle, biomarkers and atherosclerosis study

Background In the cross-sectional Lifestyle, Biomarkers, and Atherosclerosis study (LBA study) we have previously reported a high prevalence (15%) of homeostasis model assessment of insulin resistance (HOMA-IR) in Swedish, young adults. The aim of the present study was to report the dietary habits of subjects 18.0–25.9 years, and to associate dietary habits to body composition measures; body mass index (BMI), body fat (%), waist circumference and to HOMA-IR, a risk marker for diabetes. Method The subjects (577 women and 257 men) filled in a validated computerized food frequency questionnaire. The questionnaire was based on recommendations from the Swedish national food administration. To associate the dietary habits to BMI, body fat (%), waist circumference and to HOMA-IR the subjects were divided in two groups. Subjects "eating as recommended" and subjects "eating less/more than recommended". Results Recommended intake of fish and seafood (P &lt; 0.05), fruit and vegetables (P &lt; 0.001), and sweets (P &lt; 0.05) were associated to lower HOMA-IR values compared to subjects not eating as recommended. When split by sex no difference in HOMA-IR was detected with recommended intake of fish and seafood, but women eating fish and seafood as recommended had less body fat (%) (P &lt; 0.05) compared to women not eating fish and seafood as recommended. Recommended intake of fruit and vegetables was associated to lower HOMA-IR in women (P &lt; 0.01), and in women and men to less body fat (%) (P &lt; 0.05) compared to subjects not eating the recommended 500 g of fruit and vegetables per day. Both women and men with higher consumption of sweets than recommended had higher HOMA-IR (P &lt; 0.05), but no difference in the body composition measures BMI, body fat (%) or waist circumference compared to subjects eating sweets as recommended. Conclusion The results highlight the importance of reducing a high intake of sweets and to increase the intake of fish, fruit and vegetables, in young adults, to reduce the risk of future diabetes

Handgrip strength reference intervals in Swedish, young, healthy adults : The LBA study

Objectives: Handgrip strength (HGS) is a surrogate marker of general risk and nutritional status, frequently used in clinical practice. This study aimed to determine clinically useful reference intervals for healthy, young adults from Northern Europe. Methods: This cross-sectional study was conducted in central Sweden, recruiting 834 young, nonsmoking adults ages 18 to 26 y. Subjects responded to a questionnaire on general health status, medication (including contraceptives), exercise habits, and parental and their own country of birth. Anthropometry, bioimpedance analysis for determination of fat-free mass (FFM), and HGS was measured. Reference intervals were calculated as mean and standard deviation. Differences between men, women, and women using estrogen contraceptives were analyzed using an analysis of variance with Tukey's post hoc test. Associations between HGS and determinant variables were analyzed using Spearman and linear regressions. Results: Men and women differed in HGS, but no significant difference was found in average HGS based on contraceptive use in women. Mean HGS was 53 kg in men and 34 kg in women, with a range of 22 kg to 90 kg in men and 16 kg to 73 kg in women. Height correlated with HGS. Subjects with a body mass index (BMI) &lt;20 had statistically significantly lower HGS than those in higher BMI groups. There was no statistically significant mean difference between the group of subjects with a BMI of 20 to 25 and those with BMI &gt;25 in neither men nor women. HGS in both sexes showed a gradual increase through tertiles of FFM. In linear regression models, sex, height, and FFM were the main determinants of HGS. Conclusions: In this study, we established reference intervals for HGS in healthy Swedish adults ages 18 to 26 y. As a surrogate marker of whole-body muscle mass, these reference intervals can be used in health assessments and the planning of health-promoting measures in the individual young adults. Differences in HGS based on height warrant height-specific reference intervals that should be established locally

Association between C10X polymorphism in the CARD8 gene and inflammatory markers in young healthy individuals in the LBA study

Abstract Background The Caspase activation and recruitment domain 8 (CARD8) protein is a component of innate immunity as a negative regulator of NF- ĸB, and has been associated with regulation of proteins involved in inflammation. Expression of CARD8 mRNA and protein has been identified in human atherosclerotic lesions, and the truncated T30A variant (rs2043211) of CARD8 has been associated with lower C-reactive (CRP) and MCP-1 levels in myocardial infarction patients. The present study examines the role of a genetic variation in the CARD8 gene in relation to a selection of markers of inflammation. Methods In a cross-sectional study of young healthy individuals (18.0–25.9 yrs, n = 744) the association between the rs2043211 variant in the CARD8 gene and protein markers of inflammation was assessed. Genotyping of the CARD8 C10X (rs2043211) polymorphism was performed with TaqMan real time PCR on DNA from blood samples. Protein levels were studied via Olink inflammation panel ( https://olink.com/ ). Using linear models, we analyzed men and two groups of women with and without estrogen containing contraceptives separately, due to previous findings indicating differences between estrogen users and non-estrogen using women. Genotypes were analyzed by additive, recessive and dominant models. Results The minor (A) allele of the rs2043211 polymorphism in the CARD8 gene was associated with lower levels of CCL20 and IL-6 in men (CCL20, Additive model: p = 0.023; Dominant model: p = 0.016. IL-6, Additive model: p = 0.042; Dominant model: p = 0.039). The associations remained significant also after adjustment for age and potential intermediate variables. Conclusions Our data indicate that CARD8 may be involved in the regulation of CCL20 and IL-6 in men. No such association was observed in women. These findings strengthen and support previous in vitro data on IL-6 and CCL20 and highlight the importance of CARD8 as a factor in the regulation of inflammatory proteins. The reason to the difference between sexes is however not clear, and the influence of estrogen as a possible factor important for the inflammatory response needs to be further explored

Body composition is a strong predictor of local carotid stiffness in Swedish, young adults - the cross sectional Lifestyle, biomarkers, and atherosclerosis study.

BACKGROUND: Obesity has nearly tripled worldwide during the last four decades, especially in young adults, and is of growing concern since it is a risk factor for cardiovascular diseases (CVD). We explored how different body composition measurements are associated with intima media thickness (cIMT) and local stiffness in the common carotid artery, in a subsample of healthy, young women and men, from the Swedish Lifestyle, Biomarkers, and Atherosclerosis (LBA) Study. METHODS: From the LBA study, a subsample of 220 randomly selected, self-reported healthy individuals, 18-25 years old, were collected for the automatized local stiffness measurements; arterial distensibility, Young's elastic modulus, and β stiffness index. Blood pressure and mean arterial pressure (MAP) was measured using automatic blood pressure equipment. Body mass index (BMI) was calculated, waist circumference was measured, and percentage of body fat assessed using an impedance body composition analyzer. The carotid artery was scanned by ultrasound and analyzed using B-mode edge wall tracking. cIMT was measured and local stiffness measurements were calculated with carotid blood pressure, measured with applanation tonometry. RESULTS: No association was found between cIMT and body composition. Local carotid stiffness was associated with body composition, and women had less stiff arteries than men (p &lt; 0.001). Of the local stiffness measurements, arterial distensibility had the strongest associations with body composition measurements in both women and men (p &lt; 0.05). Multiple regression analyses showed that BMI in women and BMI and percentage of body fat in men had the highest impact on arterial distensibility (p &lt; 0.01 in both women and men). CONCLUSIONS: Arterial distensibility was the local stiffness measurement with the strongest associations to different body composition measurements, in both women and men. In this age group, body composition measurements seem to be stronger predictors of common carotid arterial stiffness than MAP, and is a convenient way of detecting young adults who need cardiovascular risk follow-up and lifestyle counseling

IGFBP-1 and IGFBP-2 are associated with a decreased pulse-wave velocity in young, healthy adults

Background and aims: In healthy, young adults we analyzed a panel of cardiovascular disease related proteins in plasma and compared them with the vascular health of the subjects. The aim was to identify proteins with a relationship to the early atherosclerotic process in healthy individuals. Methods: We employed the proximity extension assay from OLINK proteomics to analyze 92 cardiovascular disease (CVD) related proteins on 833 subjects (men and women, ages 18–26). The women were further divided into an estrogen-using group and non-users. Protein expression was analyzed using principal component analysis (PCA). The following vascular examinations were performed: Pulse-wave velocity (PWV), augmentation index (AIX), carotid-intima media thickness (cIMT). Results: Three principal components were obtained using PCA to analyze the protein expression. None of the obtained principal components correlated significantly with AIX or cIMT. One of the components, explaining 6% of the total variance of the data, was significantly correlated with PWV. Upon examination of the proteins with the highest factor loadings on this component independently in a multivariable model, adjusting for established CVD risk biomarkers, insulin-like growth factor-binding protein 1 (IGFBP-1) and insulin-like growth factor-binding protein 2 (IGFBP-2) were found to independently, negatively correlate with PWV. Among the established risk factors included in the multivariable model, age was significantly and adversely correlated with all vascular measurements. Conclusions: In this population of healthy, young adults, groups of CVD related proteins correlate with PWV, but not AIX or cIMT. This group of proteins, of which IGFBP-1 and IGFBP-2 were independently, negatively correlated in a multivariable model with PWV, could have benificial effects on vascular stiffness. The robust association between age and PWV, AIX and cIMT provide insight into the impact of aging on the vasculature, which is detectable even in a population of young, healthy, non-smoking individuals of ages spanning only 8 years