Subclinical Atherosclerosis in Youth: Relation to Obesity, Insulin Resistance, and Polycystic Ovary Syndrome

Abstract

ardiometabolic risk factors associated with the development of insulin resistance (IR), such as obesity, hypertension, and dyslipidemia, promote the development of atherosclerosis. These cardiovascular risk factors not only are evident in youth, but also are known to track into adulthood. Unfortunately, risk factor-related vascular changes are occurring early in life, as seen in data from autopsies performed on participants in the Bogalusa Heart Study, where adverse values of body mass index (BMI), blood pressure (BP), smoking, and serum cholesterol-specifically total, low-density lipoprotein, and high-density lipoprotein cholesterol-were associated with coronary and aortic fatty streaks in subjects aged 2-39 years. 1 Similar findings (other than an association with low-density lipoprotein cholesterol) were seen in the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) autopsy study. 2 Recent studies in youth have used noninvasive testing to demonstrate early atherosclerosis. These studies have used various modalities to differentiate "normal" and "accelerated" vascular aging by demonstrating adverse changes in the arteries in high-risk youth. In a recent article published in The Journal, Hughan et al 3 compared pulse wave velocity (PWV), a measure of arterial stiffness, and carotid intima-media thickness (cIMT), reflecting atherosclerosis, and endothelial function biomarkers among girls with obesity with and without polycystic ovary syndrome (PCOS) and healthy, normal-weight girls in a crosssectional fashion. 3 They found significantly stiffer arteries (ie, increased PWV) in the obese youth with or without PCOS compared with controls, even when adjusted for age, race, and BP (P = .002). There was no difference in cIMT among the 3 groups; however, there were differences in endothelial biomarkers, specifically VCAM-1 (P = .03). In addition, correlations between PWV and traditional cardiovascular (CV) risk factors demonstrated that PWV had the closest correlation with BMI. The authors concluded that obesity is the more important factor leading to abnormalities in vascular function in PCOS. In this review, we discuss the available evidence linking obesity-related CV risk factors in youth and the noninvasive measures of vascular structure and function.

Síndrome coronario agudo en el paciente joven

“…Estos factores de riesgo cardiovascular no solo son evidentes en la juventud, sino que siguen hasta la edad adulta. Infortunadamente, los cambios vasculares relacionados con factores de riesgo ocurren desde temprana edad, como se ve en los datos de las autopsias realizadas a los participantes en el Estudio del Corazón de Bogalusa, en quienes el índice de masa corporal, la presión arterial, el tabaquismo y los niveles de colesterol, específicamente el total de lipoproteína de baja densidad y el colesterol de lipoproteína de alta densidad, se asociaron con estrías grasas coronarias y aórticas en sujetos de 2 a 39 años 10 . Se sabe que la mayoría de los adolescentes no tienen enfermedad cardiovascular evidente; sin embargo, son muy pocos los que se encuentran libres de factores de riesgo; por ejemplo, en los adolescentes del programa SOPKARD-15, el colesterol total elevado estuvo presente en el 8% y límite en el 24%, el 8,5% tenía sobrepeso, el 7,4% eran obesos, el 5% era físicamente inactivo y el 16,4% de los niños y el 23,4% de las niñas admitían fumar 11 .…”

“…El enfoque para la prevención cardiovascular en esta población es amplio, presta atención lo antes posible a los factores sociales, familiares y de desarrollo que subyacen a los comportamientos de salud, y emplea tratamientos conductuales y farmacológicos basados en evidencia cuando sea necesario 11 . Por fortuna, la modificación del estilo de vida con dieta y ejercicio altera la historia natural de la aterosclerosis y mejora la estructura y función arterial 10 .…”

The Pediatric Obesity Microbiome and Metabolism Study (POMMS): Methods, Baseline Data, and Early Insights

“…Future analysis of the full POMMS cohort will be appropriately powered to confirm or refute this finding. However, prior research has established that obesity in children is a risk factor for cardiometabolic disease, even in the absence of clinical lab abnormalities, as demonstrated by the 2-hour glucose tolerance test, carotid intima-medial thickening, and pulse wave velocity (36). Future studies are needed to define the correlation between these candidate plasma metabolites and "clinically silent" cardiometabolic disease, both for early identification of risk and to monitor response to treatment.…”

Notes from the world congress on insulin resistance, diabetes, and cardiovascular disease

“…He suggested a risk stratification approach to select persons requiring intensive intervention, as those individuals having both prediabetes and metabolic syndrome have a many‐fold greater likelihood of progressing to diabetes . Not only is obesity a factor in adults, but Stephen Daniels, Denver, CO discussed the evidence that childhood obesity is associated with CVD, and that with recovery from metabolic syndrome there may be improvement in endothelial function . Paul Zimmet, Melbourne, Australia, who was instrumental in the development of the concept and definition of the “harmonized” metabolic syndrome, suggested an alternative central mechanism of insulin resistance, what he termed the “Circadian Syndrome” of disruption of the normal diurnal rhythm with chronic sleep insufficiency, as well as continual caloric excess, appearing to lead to epigenetic modifications eventuating in hypertension, dyslipidemia, non‐alcoholic fatty liver disease (NAFLD), sleep apnea, and perhaps depression and cognitive impairment …”

“…15 Not only is obesity a factor in adults, but Stephen Daniels, Denver, CO discussed the evidence that childhood obesity is associated with CVD, 16 and that with recovery from metabolic syndrome there may be improvement in endothelial function. 17 Paul Zimmet, Melbourne, Australia, who was instrumental in the development of the concept and definition of the "harmonized" metabolic syndrome, 18 suggested an alternative central mechanism of insulin resistance, what he termed the "Circadian Syndrome" of disruption of the normal diurnal rhythm with chronic sleep insufficiency, as well as continual caloric excess, appearing to lead to epigenetic modifications eventuating in hypertension, dyslipidemia, non-alcoholic fatty liver disease (NAFLD), sleep apnea, and perhaps depression and cognitive impairment. [19][20][21] Richard Bergman, Los Angeles, CA discussed the control of hepatic glucose production, reviewing the notion that insulin does not act directly to lower hepatic glucose production (HGP), a concept dating to the 1950s, 22 but rather that HGP is controlled indirectly by the antilipolytic effect of insulin on adipose tissue, 23 with possible additional insulin signaling through the central nervous system.…”