Cardiometabolic Disease Biomarkers Research Articles

Mineralocorticoid Receptor and Aldosterone-Related Biomarkers of End-Organ Damage in Cardiometabolic Disease.

The mineralocorticoid receptor (MR) was first identified as a blood pressure regulator, modulating renal sodium handling in response to its principal ligand aldosterone. The mineralocorticoid receptor is also expressed in many tissues other than the kidney, such as adipose tissue, heart and vasculature. Recent studies have shown that MR plays a relevant role in the control of cardiovascular and metabolic function, as well as in adipogenesis. Dysregulation of aldosterone/MR signaling represents an important cause of disease as high plasma levels of aldosterone are associated with hypertension, obesity and increased cardiovascular risk. Aldosterone displays powerful vascular effects and acts as a potent pro-fibrotic agent in cardiovascular remodeling. Mineralocorticoid receptor activation regulates genes involved in vascular and cardiac fibrosis, calcification and inflammation. This review focuses on the role of novel potential biomarkers related to aldosterone/MR system that could help identify cardiovascular and metabolic detrimental conditions, as a result of altered MR activation. Specifically, we discuss: (1) how MR signaling regulates the number and function of different subpopulations of circulating and intra-tissue immune cells; (2) the role of aldosterone/MR system in mediating cardiometabolic diseases induced by obesity; and (3) the role of several MR downstream molecules as novel potential biomarkers of cardiometabolic diseases, end-organ damage and rehabilitation outcome.

Socioeconomic inequalities in the prevalence of biomarkers of cardio-metabolic disease in South Korea: Comparison of the Health Examinees Study to a nationally representative survey.

Background/ObjectivesThis study aimed to examine socioeconomic inequalities in the prevalence of biomarkers of cardiovascular disease and diabetes in the newly developed large-scale genomic cohort study of Korean adults, the Health Examinees-Gem (HEXA-G), with a comparison of the nationally representative cross-sectional study, the Korea National Health and Nutrition Examination Survey (K-NHANES).Subjects/MethodsUsing the HEXA-G and the K-NHANES from 2007–2012, we analyzed the age-adjusted relative risk (RR) and prevalence of enlarged waist circumference (EWC), elevated triglycerides (ET), low HDL cholesterol (LHC), elevated blood pressure (EBP) and elevated blood glucose (EBG) by income and educational groups for adults at age 40–69.ResultsFor men, the prevalence of risk factors was similar across different income and educational groups (p>0.1), and between the K-NHANES and the HEXA-G. Among five risk factors, EBG showed the greatest discrepancy by 7 to 11 percentage points (i.e., the prevalence of 0.43 and 0.36 for college graduates, respectively, in K-NHANES and HEXA-G). For women, socioeconomic inequalities appeared for the five risk factors. Prevalence of risk factors was mostly lower in the HEXA-G than the K-NHANES, by approximately 11.0 percentage points. Especially, the discrepancy between K-NHANES and HEXA-G was largest in EBG (i.e., the prevalence of 0.31 and 0.20 for the lowest income groups, respectively).ConclusionThe HEXA-G shows broadly similar socioeconomic inequality in prevalence of cardio-metabolic risk factors to the nationally representative sample with more modest socioeconomic inequality among women in the HEXA-G than the K-NHANES.

ABO Genotype Does Not Modify the Association between the “Blood-Type” Diet and Biomarkers of Cardiometabolic Disease in Overweight Adults

BackgroundAlthough 7 million copies of Eat Right 4 Your Type have been sold in >60 languages, there has been a lack of evidence supporting the “blood-type” diet hypothesis. ObjectiveThe present study aimed to examine the validity of this diet in overweight adults. MethodsA total of 973 adults [mean ± SEM age: 44.6 ± 0.4 y; mean ± SEM body mass index (BMI; kg/m2): 32.5 ± 0.2; 758 women, 215 men] were participants of the Toronto Healthy Diet Study. A 1-mo, 196-item food-frequency questionnaire was used to determine dietary intakes before and after a 6-mo dietary intervention. Diet scores were calculated to determine relative adherence to each of the 4 blood-type diets as a secondary analysis. ABO blood group was determined by genotyping rs8176719 and rs8176746. ANCOVA was used to compare cardiometabolic risk factors across tertiles of diet scores. ResultsAt baseline, individuals with a higher adherence score to the type A diet had lower diastolic blood pressure (tertile 3 compared with tertile 1: 70.9 ± 1.1 compared with 73.3 ± 1.1 mm Hg; P < 0.01). Lower waist circumference was observed in individuals with higher adherence to the type B (tertile 3 compared with tertile 1: 100.8 ± 1.8 compared with 105.4 ± 1.7 cm; P < 0.01) and type AB (tertile 3 compared with tertile 1: 101.2 ± 1.8 compared with 104.8 ± 1.7 cm; P < 0.01) diets. After a 6-mo dietary intervention, individuals with increased adherence to the type A and type B diets had greater reductions in BMI and waist circumference, respectively (P < 0.01). Individuals with an increase in type O diet adherence showed decreases in both BMI and waist circumference (P < 0.01). However, matching the diets with the corresponding ABO genotype of each individual did not change the effect size of any of these associations either at baseline or at 6 mo. ConclusionABO genotype does not modify any association between blood-type diets and biomarkers of cardiometabolic disease in overweight adults, suggesting that the theory behind this diet is not valid This study was based on the data of a trial that was registered at www.clinicaltrials.gov as NCT00516620.

MicroRNAs in dysfunctional adipose tissue: cardiovascular implications.

In this review, we focus on the emerging role of microRNAs, non-coding RNAs that regulate gene expression and signaling pathways, in dysfunctional adipose tissue. We highlight current paradigms of microRNAs involved in adipose differentiation and function in depots such as white, brown, and beige adipose tissues and potential implications of microRNA dysregulation in human disease such as obesity, inflammation, microvasculature dysfunction, and related cardiovascular diseases. We highlight accumulating studies indicating that adipocyte-derived microRNAs may not only serve as biomarkers of cardiometabolic disease, but also may directly regulate gene expression of other tissues. Finally, we discuss the future prospects, challenges, and emerging strategies for microRNA delivery and targeting for therapeutic applications in cardiovascular disease states associated with adipocyte dysfunction.

Mast cells in human and experimental cardiometabolic diseases.

Mast cells, like many other types of inflammatory cell, perform pleiotropic roles in cardiometabolic diseases such as atherosclerosis, abdominal aortic aneurysms, obesity, and diabetes mellitus, as well as complications associated with these diseases. Low numbers of mast cells are present in the heart, aorta, and adipose tissue of healthy humans, but patients with cardiometabolic diseases and animals with experimentally-induced cardiometabolic pathologies have high numbers of mast cells with increased activity in the affected tissues. Mediators released by the activated mast cells, such as chemokines, cytokines, growth factors, heparin, histamine, and proteases, not only function as biomarkers of cardiometabolic diseases, but might also directly contribute to the pathogenesis of such diseases. Mast-cell mediators impede the functions of vascular cells, the integrity of the extracellular matrix, and the activity of other inflammatory cells, thereby contributing to the pathobiology of the conditions at multiple levels. In mouse models, mast-cell activation aggravates the progression of various cardiometabolic pathologies, whereas a genetic deficiency or pharmacological stabilization of mast cells, or depletion or inhibition of specific mast-cell mediators, tends to delay the progression of such conditions. Pharmacological inhibition of mast-cell activation or their targeted effector functions offers potential novel therapeutic strategies for patients with cardiometabolic disorders.

Total Worker Health Intervention Increases Activity of Sedentary Workers.

Office employees are exposed to hazardous levels of sedentary work. Interventions that integrate health promotion and health protection elements are needed to advance the health of sedentary workers. This study tested an integrated intervention on occupational sedentary/physical activity behaviors, cardiometabolic disease biomarkers, musculoskeletal discomfort, and work productivity. Two-group, RCT. Data were collected between January and August 2014. Overweight/obese adults working in sedentary desk jobs were randomized to: (1) a health protection-only group (HPO, n=27); or (2) an integrated health protection/health promotion group (HP/HP, n=27). HPO participants received an ergonomic workstation optimization intervention and three e-mails/week promoting rest breaks and posture variation. HP/HP participants received the HPO intervention plus access to a seated activity permissive workstation. Occupational sedentary and physical activity behaviors (primary outcomes), cardiometabolic health outcomes, musculoskeletal discomfort, and work productivity (secondary outcomes) were measured at baseline and post-intervention (16 weeks). The HP/HP group increased occupational light intensity physical activity over the HPO group and used the activity permissive workstations 50 minutes/work day. Significant associations were observed between activity permissive workstation adherence and improvements in several cardiometabolic biomarkers (weight, total fat mass, resting heart rate, body fat percentage) and work productivity outcomes (concentration at work, days missed because of health problems). The HP/HP group increased occupational physical activity and greater activity permissive workstation adherence was associated with improved health and work productivity outcomes. These findings are important for employers interested in advancing the well-being of sedentary office workers. This study is registered at www.clinicaltrials.gov NCT02071420.

Habitual physical activity and cardiometabolic risk factors in adults with cerebral palsy.

Adults with cerebral palsy (CP) are known to participate in reduced levels of total physical activity. There is no information available however, regarding levels of moderate-to-vigorous physical activity (MVPA) in this population. Reduced participation in MVPA is associated with several cardiometabolic risk factors. The purpose of this study was firstly to compare levels of sedentary, light, MVPA and total activity in adults with CP to adults without CP. Secondly, the objective was to investigate the association between physical activity components, sedentary behavior and cardiometabolic risk factors in adults with CP. Adults with CP (n=41) age 18-62 yr (mean ± SD=36.5 ± 12.5 yr), classified in Gross Motor Function Classification System level I (n=13), II (n=18) and III (n=10) participated in this study. Physical activity was measured by accelerometry in adults with CP and in age- and sex-matched adults without CP over 7 days. Anthropometric indicators of obesity, blood pressure and several biomarkers of cardiometabolic disease were also measured in adults with CP. Adults with CP spent less time in light, moderate, vigorous and total activity, and more time in sedentary activity than adults without CP (p<0.01 for all). Moderate physical activity was associated with waist-height ratio when adjusted for age and sex (β=-0.314, p<0.05). When further adjustment was made for total activity, moderate activity was associated with waist-height ratio (β=-0.538, p<0.05), waist circumference (β=-0.518, p<0.05), systolic blood pressure (β=-0.592, p<0.05) and diastolic blood pressure (β=-0.636, p<0.05). Sedentary activity was not associated with any risk factor. The findings provide evidence that relatively young adults with CP participate in reduced levels of MVPA and spend increased time in sedentary behavior, potentially increasing their risk of developing cardiometabolic disease.

Abstract P206: Estimation of Directly Quantified Visceral Adipose Tissue Using Cardiometabolic Biomarkers

Background: Visceral adipose tissue (VAT) has been linked to increased cardiovascular (CV) risk. Furthermore, there is limited data on how anthropometric measures and known markers of cardiometabolic disease (CMD) relate to the presence of VAT. Therefore, the aim of this study was to define how CMD biomarkers relate to directly-quantified volume-based measures of VAT using computed tomography (CT) scan measurements in a well-phenotyped sample of patients from an ongoing cohort study of inflammation and CMD. Methods and Results: We evaluated the relationship between directly measured VAT, anthropometric measures [body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR)] and CMD biomarkers [lipoproteins, lipoprotein particle size, high sensitivity C-reactive protein (hsCRP), insulin resistance markers] in a longitudinal study of CV risk predictors in chronic inflammation (NCT: NCT01778569). Patients underwent blood testing and CT to measure the sum of visceral adipose tissue between the diaphragm and the inferior border of the urinary bladder (slice 50-150 SumVAT) during a single baseline visit in 2012-2013 (N=42), resulting in a validated, volume-based measurement of VAT. Linear regression modeling was used to understand the relationship between VAT, anthropometric measures and CMD biomarkers. Those with higher levels of visceral adiposity were more likely to be male (p=0.05) and have higher BMI. Adjusting for age, sex, race, physical activity, smoking, and CV risk factors, HDL, hsCRP, insulin, and HOMA-IR were independent predictors of 50-150 SumVAT (Table). Conclusions: Markers of lipid metabolism, inflammation, and insulin resistance serve as independent predictors of visceral adiposity and may be useful surrogates to estimate VAT when volume-based CT measures are not possible. Therefore, these biomarkers may be used to evaluate cardio-metabolic risk in areas with limited access to imaging for defining visceral adiposity, particularly community-based settings.

Plasma vitamin D, hormonal contraceptive use, and biomarkers of cardiometabolic disease

The relationship between vitamin D and cardiometabolic disease is unclear. Hormonal contraceptive (HC) use among women is associated with elevated plasma 25‐hydroxyvitamin D [25(OH)D]. HC use is also associated with cardiometabolic disease risk. The objective was to examine whether the association between 25(OH)D and biomarkers of cardiometabolic disease differs between healthy young women HC non‐users (n=677), women HC users (n=280), and men (n=427) aged 20 – 29 years. Participants provided overnight fasting blood samples for measurement of 25(OH)D, glucose, insulin, and blood lipids. HC use was determined by questionnaire. In models adjusted for age, waist circumference, physical activity, ethnicity, and season of blood collection, vitamin D deficiency was associated with higher insulin, HOMA‐IR, and HOMA‐Beta among men and women HC non‐users, and with higher triglycerides among men only. No biomarkers were associated with 25(OH)D among women HC users. Circulating 25(OH)D concentrations are inversely associated with biomarkers of glycemic dysregulation in young adults; however, HC use among women attenuates this association. Given the widespread use of HC by women throughout the world, a better understanding of the extent to which these medications modify the relationship between vitamin D and disease‐related processes is warranted. Research support from the Advanced Foods and Materials Network.Grant Funding Source: Advanced Foods and Materials Network

Genetic Variation in the Vitamin D Receptor, Plasma 25-Hydroxyvitamin D, and Biomarkers of Cardiometabolic Disease in Caucasian Young Adults

Background/Aims: Vitamin D regulates gene transcription by binding to the vitamin D receptor (VDR), potentially affecting cardiometabolic disease risk. However, studies of 25-hydroxyvitamin D [25(OH)D] and cardiometabolic disease are inconsistent. Inconsistencies may result from unaccounted for interactions between VDR genetic variants and 25(OH)D. We examined the effect of 25(OH)D on the association between VDR variants and cardiometabolic disease biomarkers. Methods: The relationship between 25(OH)D, 24 VDR variants, and 10 cardiometabolic biomarkers was examined in 488 Caucasians aged 20-29 years. Covariate-adjusted general linear models were used to examine the interaction effect of 25(OH)D × VDR on each biomarker. When interactions were significant (p < 0.05), relationships were further examined with analysis of covariance, stratified by tertiles of 25(OH)D and adjusted for multiple comparisons. Results: In the lowest tertile of 25(OH)D, major allele homozygotes for rs3819545 had higher insulin and HOMA-IR than minor allele carriers (p ≤ 0.002). Fasting insulin and HOMA-IR were lower in the highest than the lowest tertile of 25(OH)D among major allele homozygotes (p < 0.0001), but minor allele carriers had similar levels regardless of vitamin D status. Conclusions: We identified 25(OH)D-dependent associations between rs3819545 and glycemic dysregulation biomarkers. Major allele homozygotes with low vitamin D status may be at increased risk of insulin resistance.

The association between obesity, cardiometabolic disease biomarkers, and innate immunity-related inflammation in Canadian adults

IntroductionObesity is associated with a state of chronic inflammation, and increased cardiometabolic disease risk. The present study examined the relationship between body mass index (BMI) and cardiometabolic and inflammatory biomarkers among normal weight, overweight, and obese Canadian adults.MethodsSubjects (n = 1805, aged 18 to 79 years) from the Canadian Health Measures Survey (CHMS) were examined for associations between BMI, cardiometabolic markers (apolipoprotein [Apo] A1, ApoB, low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], total cholesterol, total cholesterol/HDL ratio [total:HDL-C ratio], triglycerides, and glycosylated hemoglobin [HbA1c]), inflammatory factors (C-reactive protein [CRP], fibrinogen, and homocysteine), and 25-hydroxyvitamin D [25(OH)D]. Bootstrap weights for variance and sampling weights for point estimates were applied to account for the complex survey design. Linear regression models adjusted for age, sex, physical activity, smoking status, and ethnicity (in addition to season of clinic visit, for vitamin D analyses only) were used to examine the association between cardiometabolic markers, inflammatory factors, and BMI in Canadian adults.ResultsAll biomarkers were significantly associated with BMI (P ≤ 0.001). ApoA1 (β = −0.31, P < 0.0001), HDL-C (β = −0.61, P < 0.0001), and 25(OH)D (β = −0.25, P < 0.0001) were inversely associated with BMI, while all other biomarkers showed positive linear associations. Distinct patterns of association were noted among normal weight, overweight, and obese groups, excluding CRP which showed a significant positive association with BMI in the overall population (β = 2.80, P < 0.0001) and in the normal weight (β = 3.20, P = 0.02), overweight (β = 3.53, P = 0.002), and obese (β = 2.22, P = 0.0002) groups.ConclusionsThere is an apparent profile of cardiometabolic and inflammatory biomarkers that emerges as BMI increases from normal weight to obesity. Understanding these profiles may permit developing an effective approach for early risk prediction for cardiometabolic disease.

Circulating leukocyte telomere length is highly heritable among families of Arab descent

BackgroundTelomere length, an indicator of ageing and longevity, has been correlated with several biomarkers of cardiometabolic disease in both Arab children and adults. It is not known, however, whether or not telomere length is a highly conserved inheritable trait in this homogeneous cohort, where age-related diseases are highly prevalent. As such, the aim of this study was to address the inheritability of telomere length in Saudi families and the impact of cardiometabolic disease biomarkers on telomere length.MethodsA total of 119 randomly selected Saudi families (123 adults and 131 children) were included in this cross-sectional study. Anthropometrics were obtained and fasting blood samples were taken for routine analyses of fasting glucose and lipid profile. Leukocyte telomere length was determined using quantitative real time PCR.ResultsTelomere length was highly heritable as assessed by a parent-offspring regression [h2 = 0.64 (p = 0.0006)]. Telomere length was modestly associated with BMI (R2 0.07; p-value 0.0087), total cholesterol (R2 0.08; p-value 0.0033), and LDL-cholesterol (R2 0.15; p-value 3 x 10-5) after adjustments for gender, age and age within generation.ConclusionThe high heritability of telomere length in Arab families, and the associations of telomere length with various cardiometabolic parameters suggest heritable genetic fetal and/or epigenetic influences on the early predisposition of Arab children to age-related diseases and accelerated ageing.

Self-Rated Health in middle-aged and elderly Chinese: distribution, determinants and associations with cardio-metabolic risk factors

BackgroundSelf-rated health (SRH) has been demonstrated to be an accurate reflection of a person's health and a valid predictor of incident mortality and chronic morbidity. We aimed to evaluate the distribution and factors associated with SRH and its association with biomarkers of cardio-metabolic diseases among middle-aged and elderly Chinese.MethodsSurvey of 1,458 men and 1,831 women aged 50 to 70 years, conducted in one urban and two rural areas of Beijing and Shanghai in 2005. SRH status was measured and categorized as good (very good and good) vs. not good (fair, poor and very poor). Determinants of SRH and associations with biomarkers of cardio-metabolic diseases were evaluated using logistic regression.ResultsThirty two percent of participants reported good SRH. Males and rural residents tended to report good SRH. After adjusting for potential confounders, residence, physical activity, employment status, sleep quality and presence of diabetes, cardiovascular disease, and depression were the main determinants of SRH. Those free from cardiovascular disease (OR 3.68; 95%CI 2.39; 5.66), rural residents (OR 1.89; 95% CI 1.47; 2.43), non-depressed participants (OR 2.50; 95% CI 1.67; 3.73) and those with good sleep quality (OR 2.95; 95% CI 2.22; 3.91) had almost twice or over the chance of reporting good SRH compared to their counterparts. There were significant associations -and trend- between SRH and levels of inflammatory markers, insulin levels and insulin resistance.ConclusionOnly one third of middle-aged and elderly Chinese assessed their health status as good or very good. Although further longitudinal studies are required to confirm our findings, interventions targeting social inequalities, lifestyle patterns might not only contribute to prevent chronic morbidity but as well to improve populations' perceived health.

Sleep quality in middle-aged and elderly Chinese: distribution, associated factors and associations with cardio-metabolic risk factors

BackgroundPoor sleep quality has been associated with increased risk of heart disease, diabetes and mortality. However, limited information exists on the distribution and determinants of sleep quality and its associations with cardio-metabolic risk factors in Chinese populations. We aimed to evaluate this in the current study.MethodsA cross-sectional survey conducted in 2005 of 1,458 men and 1,831 women aged 50–70 years from urban and rural areas of Beijing and Shanghai. Using a questionnaire, sleep quality was measured in levels of well, common and poor. Comprehensive measures of socio-demographical and health factors and biomarkers of cardio-metabolic disease were recorded. These were evaluated in association with sleep quality using logistic regression models.ResultsHalf of the population reported good sleep quality. After adjusting for potential confounders, women and Beijing residents had almost half the probability to report good sleep quality. Good physical and mental health (good levels of self-rated health (OR 2.48; 95%CI 2.08 to 2.96) and no depression (OR 4.05; 95%CI 3.12 to 5.26)) related to an increased chance of reporting good sleep quality, whereas short sleep duration (<7 hrs OR 0.10; 95%CI 0.07 to 0.14)) decreased it substantially. There were significant associations between levels of sleep quality and concentrations of plasma insulin, total and LDL cholesterol, and index of insulin resistance.ConclusionLevels of good sleep quality in middle-age and elderly Chinese were low. Gender, geographical location, self-rated health, depression and sleep quantity were major factors associated with sleep quality. Prospective studies are required to distil the factors that determine sleep quality and the effects that sleep patterns exert on cardio-metabolic health.