Elevated blood pressure-associated cardiometabolic risk factors and biomarkers in 16-23 years old students with or without metabolic abnormalities.

In obesity, cardiometabolic risk markers show worsening trends with increasing blood pressure (BP). We assumed that risk markers show similar trends across BP categories (normotension, high normal BP, hypertension) in metabolic abnormalities-free subjects (without obesity, insulin resistance, atherogenic dyslipidemia, hyperuricemia, microinflammation) and those presenting them. Data from 2547 (48.1% males) subjects aged 16-23 years were analyzed. The prevalence of males increased across BP categories. Forty-seven percent of individuals with elevated BP were metabolic abnormalities-free. Among 1461 metabolic abnormalities-free subjects, 9% had high normal BP, and 4% hypertension; among 1086 individuals presenting metabolic abnormalities, the prevalence reached 13% and 6%, respectively, (p < 0.001). Both groups displayed similar BP values in corresponding BP categories and significant trends in markers of adiposity, insulin resistance, HDL-cholesterol, atherogenic index of plasma, uric acid, adiponectinemia, and antioxidant capacity of plasma across BP categories. In metabolic abnormalities-free individuals, also significant trends in soluble receptors for advanced glycation end products were revealed. Continuous metabolic syndrome score, a measure of cardiometabolic risk, increased across BP categories regardless of presence or absence of metabolic abnormalities. Multivariate regression models selected male gender, fat-free mass, and uric acid as significant independent predictors for determining BP. Our data emphasize that having a BP outside the normal range significantly worsens risk for cardiometabolic disease in young individuals even if the thresholds for any of the risk factors are not exceeded. Longitudinal studies are needed to assess whether in patients with elevated BP the prognosis of adverse outcomes differs between those presenting and not presenting metabolic abnormalities.

Sex Differences in Association of Elevated Blood Pressure with Variables Characterizing Cardiometabolic Risk in Young Subjects with or Without Metabolic Abnormalities.

Males present higher blood pressure (BP) values, higher prevalence of elevated BP, and a different prevalence of cardiometabolic risk factors when compared with females. We assumed that the trends of risk markers across BP categories (normotension, high normal BP, and hypertension) differ in young males and females, and between subjects without metabolic abnormalities (without obesity, insulin resistance, atherogenic dyslipidemia, hyperuricemia, or microinflammation) and those presenting them. Data from 2543 subjects (48% males) aged from 16 to 23 years were analyzed. The findings showed that 15% of males and 4% of females presented high normal BP while 9% and 1%, respectively, had hypertension. In males, variables characterizing obesity status, insulin sensitivity, atherogenic dyslipidemia, uric acid, adiponectin, a soluble receptor for advanced glycation end-products, and leukocyte counts showed worsening trends across BP categories. Females presented significant trends only for obesity measures, LDL-cholesterol, and non-HDL-cholesterol. Across BP categories, trends of variables characterizing cardiometabolic risk differed among abnormalities-free and presenting males. The multivariate model selected measures of central obesity, atherogenic dyslipidemia, insulin resistance, and uric acid as significant predictors of BP in both genders, and C-reactive protein in females. Sex differences in measures of cardiovascular health in juveniles may remain undiscovered unless two sexes are analyzed separately. These differences may have implications for sex-specific disease risk in adulthood.

Estimation of the proportion of metabolic syndrome-free subjects on high cardiometabolic risk using two continuous cardiometabolic risk scores: a cross-sectional study in 16- to 20-year-old individuals.

In contrast to the dichotomous classification of metabolic syndrome, continuous metabolic syndrome scores enable to assess cardiometabolic burden in metabolic syndrome-free individuals. Using receiver operating characteristics analysis, discrimination power of continuous metabolic syndrome score calculated from population-based Z-scores or individual measures corrected to the accepted international standards for presence/absence of metabolic syndrome was assessed. Calculated cutoff values were used to estimate the proportions of metabolic syndrome-free subjects presenting high cardiometabolic risk. Clinical data were collected from 2331 (52% females) 16- to 20-year-old subjects. Receiver operating characteristics analyses showed an acceptable performance of both scores to classify metabolic syndrome presence: area under the curve (97-98%), sensitivity (95-100%), and specificity (86-96%). Compared with the prevalence of metabolic syndrome, proportions of metabolic syndrome-free subjects on high cardiometabolic risk, e.g., presenting continuous scores ≥ cutoff points, were about 3-fold higher in males, and 4-fold higher in females. Both scores correlated significantly with markers of cardiometabolic risk.Conclusion: Continuous cardiometabolic syndrome scores are practical tools to evaluate cardiometabolic risk in subjects not presenting metabolic syndrome. Accuracy, simplicity, and ability to classify metabolic syndrome-free subjects on high cardiometabolic risk make continuous metabolic syndrome score derived from international standards convenient for use in research and clinical practice. What is Known: • Dichotomous classification of metabolic syndrome is simple but not suitable for assessment of cardiometabolic burden in metabolic syndrome-free subjects. This prompted implementation of continuous scores, which are generally sample-specific. Score based on internationally accepted standards allows for comparison between populations and studies. • The performance of different continuous metabolic syndrome scores to assess the prevalence of metabolic syndrome-free subjects presenting high cardiometabolic burden has not been compared yet. What is New: • We compared the discrimination power of sample-specific Z-score-derived continuous metabolic syndrome score and that calculated based on internationally accepted standards for presence or absence of metabolic syndrome in young subjects. • The prevalence of metabolic syndrome-free subjects presenting high cardiometabolic risk was estimated using the cutoff points of continuous metabolic syndrome scores derived from the analyses of receiver operating characteristic curves.

Gender Differences in Cardiometabolic Risk Factors in Metabolically Healthy Normal Weight Adults with Central Obesity.

We investigated whether metabolically healthy normal weight adults with central obesity display worse cardiometabolic profile compared with their centrally lean counterparts. This retrospective, cross-sectional study, comprised 1 135 subjects (64% females) aged 18-to-81 years, presenting ≤2 components of metabolic syndrome. They were classified as centrally lean (waist-to-height ratio (WHtR)<0.5 and waist circumference<80 cm in females and<94 cm in males) or presenting central obesity (WHtR ≥0.5, regardless of waist circumference). Data on blood pressure, glucose homeostasis, lipid profile, renal function, high-sensitive C-reactive protein (hsCRP), uric acid, adiponectin, leptin, and soluble receptor for advanced glycation end products were compared between the groups, separately in males and females. 5.7% of males and 6.9% of females presented WHtR ≥0.5. Compared with centrally lean subjects, those with central obesity had higher BMI-adjusted fasting plasma glucose (p<0.001), and leptin levels (p<0.05); females also presented higher blood pressure (p<0.001), while males had higher hsCRP concentrations (p=0.021). These changes associated with significantly higher BMI-adjusted odds to present fasting plasma glucose >5.6 mmol/l in both genders, higher odds to present hsCRP >3 mg/l in males, and those to present elevated blood pressure in females. Our analysis suggests that in metabolically healthy normal weight subjects WHtR ≥0.5 might indicate "early increased health risk".

Correlation among soluble receptors for advanced glycation end-products, soluble vascular adhesion protein-1/semicarbazide-sensitive amine oxidase (sVAP-1) and cardiometabolic risk markers in apparently healthy adolescents: a cross-sectional study.

In non-diabetics, low levels of soluble receptor for advanced glycations end products (sRAGE) associate with an increased risk of development of diabetes, cardiovascular afflictions, or death. The majority of studies in non-diabetics report an inverse relationship between measures of obesity, cardiometabolic risk factors and sRAGE and/or endogenous secretory RAGE (esRAGE) levels. To elucidate whether this inconsistency is related to the metabolically healthy obese phenotype, or a different impact of the risk factors in presence and absence of obesity, we analyzed data from 2206 apparently healthy adolescents (51 % girls) aged 15-to-19 years. The association of sRAGE levels with soluble vascular adhesion protein-1/semicarbazide sensitive amine oxidase (sVAP-1/SSAO) was also investigated. Centrally obese, including metabolically healthy, adolescents present significantly lower sRAGE and esRAGE, but not sVAP-1, levels in comparison with their lean counterparts. An increasing number of cardiometabolic risk factors did not associate with significant changes in sRAGE, esRAGE or sVAP-1 levels either in lean or in obese subjects. In multivariate analyses, WHtR, hsCRP, markers of glucose homeostasis, renal function, adiponectin, and sVAP-1 associated significantly with sRAGE and esRAGE. SVAP-1 correlated significantly with glycemia, adiponectin, hsCRP, and sRAGE. Thus, in adolescents, a decline in sRAGE and esRAGE precedes the development of metabolic syndrome. When combined, standard and non-standard cardiometabolic risk factors explain only minor proportion in a variability of sRAGE and esRAGE (8 %-11 %); or sVAP-1 (12 %-20 %). Elucidation of pathogenetic mechanisms underlying early decline in sRAGE and esRAGE levels in obese adolescents and their clinical impact with regard to future cardiometabolic health requires further studies.

Presence of Cardiometabolic Risk Factors Is Not Associated with Microalbuminuria in 14-to-20-Years Old Slovak Adolescents: A Cross-Sectional, Population Study.

INTRODUCTION: In adults, microalbuminuria indicates generalized endothelial dysfunction, and is an independent risk factor for cardiovascular and all cause mortality. Slovak adults present one of the highest cardiovascular mortality rates in Europe. Thus Slovak adolescents are on a high-risk to develop cardiovascular afflictions early, and screening for microalbuminuria might be useful in early assessment of their cardiovascular risk. We aimed to study the prevalence of microalbuminuria in Slovak adolescents, and the association of urinary albumin-to-creatinine ratio (ACR) to cardiovascular risk factors. SUBJECTS AND METHODS: Anthropometric data, blood pressure, blood count, glucose homeostasis, lipid profile, renal function, inflammatory status, concentrations of homocysteine and uric acid were determined and associated with ACR in 2 666 adolescents (49.4% boys, 51.6% girls) aged 14-to-20 years. Microalbuminuria was classified as ACR 2.5-25.0 mg/mmol in boys and 3.5-35.0 mg/mmol in girls. RESULTS: Prevalence of microalbuminuria in both genders reached 3.3%, and did not differ significantly between lean and centrally obese subjects. Girls presented higher ACR than boys (normoalbuminuric: 0.6 ± 0.5 mg/mmol vs. 0.5 ± 0.4 mg/mmol, p > 0.001; microalbuminuric: 9.3 ± 7.3 mg/mmol vs. 5.0 ± 3.8 mg/mmol; p > 0.001). Microalbuminuric adolescents and those presenting normoalbuminuria within the upper ACR quartile were slimmer than their normoalbuminuric counterparts or adolescents with normoalbuminuria within the lower quartile, respectively. No association between microalbuminuria and cardiovascular risk markers was revealed. CONCLUSION: Results obtained in this study do not support our assumption that ACR associates with cardiometabolic risk factors in apparently healthy adolescents. Follow-up studies until adulthood are needed to estimate the potential cardiometabolic risk of apparently healthy microalbuminuric adolescents.