Origins Of Cardiovascular Disease Research Articles

Developmental Origins of Cardiovascular Disease: Understanding High Mortality Rates in the American South.

While many social scientists view heart disease as the outcome of current conditions, this cannot fully explain the significant geographic disparities in cardiovascular disease (CVD) mortality rates in the USA. The developmental origins hypothesis proposes that CVD vulnerability is created by poor conditions in utero that underbuilds major organs relative to those needed to process lush nutrition later in life. The American South underwent an economic transformation from persistent poverty to rapid economic growth in the post-World War II era. We use state-level data on income growth and current conditions to explain variation in CVD mortality rates in 2010–2011. Our proxy for unbalanced physical growth, the ratio of median household income in 1980 to that in 1950, has a large systematic influence on CVD mortality, an impact that increases dramatically with age. The income ratio combined with smoking, obesity, healthcare access, and education explain more than 70% of the variance in CVD mortality rates.

Complicaciones cardiovasculares en relación con la programación fetal

Introducción: la programación fetal ofrece nuevas perspectivas sobre el origen de las enfermedades cardiovasculares, relacionando su aparición con factores perinatales. Objetivo: exponer evidencia que vincule las alteraciones gestacionales con las enfermedades cardiovasculares en la vida adulta del feto. Metodología: búsqueda en las bases de datos EBSCO, COCHRANE, MEDLINE, PROQUEST y SciELO de los artículos de revisión e investigaciones originales en inglés publicados en los últimos diez años. Se utilizaron términos MeSH para búsqueda controlada y se evaluaron los estudios con STROBE y PRISMA según correspondía. Resultados: los hallazgos sugieren que nacer con menos de 2600 k guarda relación con diabetes mellitus (OR de 1.607 IC 95% 1.324-1.951), hipertensión arterial (OR de 1.15 IC 95% 1.043-1.288) y menor función endotelial (1.94+0.37 vs 2.68+0.41, p: 0.0001) en la adultez. La prematuridad se asocia con mayores presiones arteriales sistólicas (4.2 mmHg IC 95%; 2.8 - 5.7 p 0.001) y diastólicas (2.6 mmHg IC 95%; 1.2-4.0; p 0.001). Las alteraciones nutricionales maternas y la diabetes gestacional aumentan el riesgo de síndrome metabólico (OR 1.2 IC 95% 0.9-1.7) y sobrepeso en la edad escolar (OR 1.81 IC 95% 1.18 - 2.86). Conclusión: los resultados adversos en la gestación están relacionados con el desarrollo de enfermedades cardiovasculares en la vida adulta del feto expuesto.

The Cardiovascular Stress Response as Early Life Marker of Cardiovascular Health: Applications in Population-Based Pediatric Studies\u2014A Narrative Review

Stress inducement by physical exercise requires major cardiovascular adaptations in both adults and children to maintain an adequate perfusion of the body. As physical exercise causes a stress situation for the cardiovascular system, cardiovascular exercise stress tests are widely used in clinical practice to reveal subtle cardiovascular pathology in adult and childhood populations with cardiac and cardiovascular diseases. Recently, evidence from small studies suggests that the cardiovascular stress response can also be used within research settings to provide novel insights on subtle differences in cardiovascular health in non-diseased adults and children, as even among healthy populations an abnormal response to physical exercise is associated with an increased risk of cardiovascular diseases. This narrative review is specifically focused on the possibilities of using the cardiovascular stress response to exercise combined with advanced imaging techniques in pediatric population-based studies focused on the early origins of cardiovascular diseases. We discuss the physiology of the cardiovascular stress response to exercise, the type of physical exercise used to induce the cardiovascular stress response in combination with advanced imaging techniques, the obtained measurements with advanced imaging techniques during the cardiovascular exercise stress test and their associations with cardiovascular health outcomes. Finally, we discuss the potential for cardiovascular exercise stress tests to use in pediatric population-based studies focused on the early origins of cardiovascular diseases.

Preserving Optimal Cardiovascular Health in Children.

The origins of cardiovascular disease are at the beginning of life, and national guidelines recommend evaluation for cardiovascular risk factors such as obesity and hypertension as part of general pediatric care. In this review, a simple plan is proposed for clear and consistent monitoring and messaging throughout childhood, based on the American Heart Association's "cardiovascular health" construct. A framework is provided for age-appropriate scoring of the cardiovascular health components, including diet, physical activity and screen time, sleep, smoking exposure, body mass index, blood pressure, cholesterol, and glucose. Guidance is provided for evidence-based, efficient intervention by pediatric clinicians to preserve or restore cardiovascular health. Finally, anticipated near-term advances in pediatric cardiovascular health promotion are previewed. [Pediatr Ann. 2018;47(12):e479-e486.].

Prevalencia de adiposidad corporal y dislipidemia en funcionarios de la Policía Nacional Bolivariana de la Universidad Nacional Experimental de la Seguridad

Introducción: La composición corporal es uno de los elementos clave en el desarrollo de la labor operacional del funcionario policial, que, con un elevado porcentaje de adiposidad corporal, resultarían muy difícil su desempeño, asimismo, los individuos con un exceso de masa grasa exhiben comúnmente un perfil lipídico alterado denominado dislipidemia aterogénica, estando ambos parámetros asociados al origen de enfermedades cardiovasculares (ECV). En éste estudio, se investiga la prevalencia de adiposidad corporal e irregularidades lipídicas y la relación entre estos como factores de riesgo asociados con las ECV en un grupo de funcionarios de la Policía Nacional Bolivariana.Material y Métodos: La muestra la conformaron 45 hombres y 20 mujeres. Se calculó el Índice de Masa Corporal (IMC) y el porcentaje de grasa (%GC) como indicadores adiposos y el perfil lipídico como indicadores bioquímicos. Resultados: Ambos grupos se ubicaron en categorías superiores a las recomendadas, obteniendo los hombres y mujeres un IMC y un %GC de 29,7 y 27,6% y 25,6 y 33,4%, ambos con diferencias significativas. De la misma forma, las mujeres superaron el límite superior de triglicéridos con 151,8 mg/dL, y estando cerca del límite superior del colesterol y a su vez, obtuvieron valores inferiores del HDL-c (40,5 mg/dL). Un porcentaje importante de ambos grupos presentó alteración en los indicadores bioquímicos a excepción del c-LDL. El colesterol y los triglicéridos tuvieron moderada correlación con el IMC en las mujeres, y moderadas, bajas y correlaciones inversas entre los parámetros de perfil lipídico con el IMC y el %GC en los hombres. Conclusiones: Se concluye que un importante porcentaje de funcionarios, muestran alta adiposidad, y ésta, relacionada con alteraciones en los lípidos, puede incrementar el riesgo para el desarrollo de ECV.

Risk factors for cardiovascular disease in children and young adults with haemophilia.

The origins of cardiovascular disease (CVD) begin in childhood. The primary objective of this cross-sectional cohort study was to determine the prevalence of cardiovascular risk factors in patients with congenital haemophilia A or B followed at Rady Children's Hospital San Diego Hemophilia and Thrombosis Treatment Center (HTC). We hypothesized that cardiovascular risk factors could be identified as part of a comprehensive clinic visit. Standardized measurement of weight, height, waist circumference and blood pressure plus non-fasting glucose and lipid panel were performed. Participants and/or caregivers completed questionnaires about family history, medical history and lifestyle. Clinical data were abstracted from the medical record. Descriptive statistics, Student's t test, correlation, Mann-Whitney U test and chi-square test were performed to analyse the data. Forty-three males (mean 12years, range 5-20years) enrolled. High rates of overweight and obesity, (pre)hypertension and abnormal lipids were identified. Subjects with normal weight had more days of >60minutes of physical activity compared with those with overweight or obesity (5.2±2.4 vs. 3.8±2.5day; P=0.07). Higher weight was correlated with higher factor consumption (cor=0.88; P<0.001). There was no difference in target joints based on weight category (30% in normal weight vs. 25% in overweight or obese, χ2 = 0.11, P=0.74), which may be attributed to high rates of prophylaxis. Modifiable risk factors for CVD were identified as part of the study during comprehensive clinic visits. The HTC team may develop behavioural interventions to target cardiovascular risk reduction as part of the comprehensive care model.

Reference Intervals for Non-Fasting CVD Lipids and Inflammation Markers in Pregnant Indigenous Australian Women.

Indigenous Australians experience high rates of cardiovascular disease (CVD). The origins of CVD may commence during pregnancy, yet few serum reference values for CVD biomarkers exist specific to the pregnancy period. The Gomeroi gaaynggal research project is a program that undertakes research and provides some health services to pregnant Indigenous women. Three hundred and ninety-nine non-fasting samples provided by the study participants (206 pregnancies and 175 women) have been used to construct reference intervals for CVD biomarkers during this critical time. A pragmatic design was used, in that women were not excluded for the presence of chronic or acute health states. Percentile bands for non-linear relationships were constructed according to the methods of Wright and Royston (2008), using the xriml package in StataIC 13.1. Serum cholesterol, triglycerides, cystatin-C and alkaline phosphatase increased as gestational age progressed, with little change seen in high-sensitivity C-Reactive Protein and γ glutamyl transferase. Values provided in the reference intervals are consistent with findings from other research projects. These reference intervals will form a basis with which future CVD biomarkers for pregnant Indigenous Australian women can be compared.

Management of different cardiovascular risk factors with acombination tablet (polypill)

The multifactorial origin of cardiovascular diseases has led to polypharmacy in primary and secondary prophylaxis with evidence-based medications, such as statins, antihypertensive drugs and platelet aggregation inhibitors. The number of prescribed drugs correlates inversely to adherence and can lead to treatment failure. Fixed-dose combination drugs (polypills) could increase the medication adherence of patients, reduce risks and prevent cardiovascular events. This review is based on publications that were retrieved from Medline (via PubMed) and The Cochrane Library. The clinical database ClinicalTrials.gov. was also considered. In the studies on primary prevention conducted to date, fixed-dose combinations showed asuperior control of risk factors, e.g. hypertension and low-density lipoprotein (LDL) cholesterol compared to placebo and at least non-inferiority compared to usual care. In secondary prevention, the effect of the polypill is mostly on the reduction of blood pressure and LDL cholesterol in non-adherent patients; however, evidence that fixed-drug combinations reduce cardiovascular morbidity and mortality compared to standard therapy is lacking. The polypill can be considered as an alternative to polypharmacy after a risk-benefit assessment, especially in non-adherent patients. Ongoing studies are investigating the effect of the polypill on cardiovascular events. Current polypills are limited by the lack of sufficient dosages of the individual components to avoid overtreatment and undertreatment at the individual treatment level.

Arterial Stiffness, Thickness and Association to Suitable Novel Markers of Risk at the Origin of Cardiovascular Disease in Obese Children.

Atherosclerosis origins early in childhood. Aim of the study was to investigate vascular signature and phenotypes of cardiovascular disease in obese children and adolescents identifying novel potential circulating markers of risk.Cross-sectional study of intima-media-thickness (IMT), pulse wave velocity (PWV), augmentation index (AIX@75), circulating markers (E-selectin, soluble-intercellular-adhesion-molecule1_ICAM1, chemerin, fatty-acid-binding protein 4, sCD36, lipopolysaccharides_LPS, oxLDL, fetuin) in 123 obese (body mass index, BMI z-score >1.645 SD) children (N=55, age ≤10 years-old) and adolescents (N=68, age >10 years-old).Adolescents had significantly higher uric acid (p=0.002), non-HDL-cholesterol (p=0.02), fasting glucose (p=0.04), systolic blood pressure (p=0.005) and PWV (p=0.02) than children.Obese adolescent patients with metabolic syndrome (MetS) abnormalities had higher PWV (p<0.05) than peers without. No differences were observed in circulating biomarkers in relationship to age and MetS status. oxLDL, sCD36 and LPS were correlated to AIX@75 and/or IMTM in children and adolescents (p ranging from <0.05 to <0.0001). Total cholesterol, non-HDL-cholesterol, TG/HDL ratio, oxLDL, sCD36, ICAM1, LPS were significantly different across AIX@75 tertiles (p between 0.03 and 0.001).Early phenotypes of cardiovascular alterations in young severely obese patients encompass increased IMT, stiffness of intermediate size and resistance vasculature. Novel biomarkers investigated in the present study were associated to estimates of stiffness and thickness not differently from traditional risk factor such as non-HDL-cholesterol and TG/HDL ratio.

Metabolic Syndrome and Associated Factors in Adults of the Amazon Region.

Metabolic syndrome (MS) plays a key role in the origin of cardiovascular diseases. Studies on the MS in Brazil are recent, and its epidemiology in more isolated regions such as the Amazon is still unknown. The study aimed to estimate the prevalence of MS and associated factors in adults of the Brazilian Amazon. This study was conducted in 2012–2013. It is a cross-sectional population-based study, involving 787 adults randomly selected from the urban area of four cities in the state of Pará, in the Brazilian Eastern Amazon. The participants underwent anthropometric measurements, laboratory examination, and were questioned about their lifestyle. MS was defined by the Joint Interim Statement criteria, using the multiple logistic regression to investigate the potential association of risk factors with the presence of MS. The overall prevalence of MS was 34.1% (95% CI = 30.8–37.4), increasing linearly with the increasing body mass index and age. From 40–49 years of age, MS was observed in about half of the women (46.0%), while men only experienced a high prevalence in the fifth decade of life (43.3%). The low HDL-c (64.4%) and abdominal obesity (58.9%) were higher in women (p < 0.001), while for men, high blood pressure was significantly higher (p < 0.001). Individuals aged 40–59 years old (odds ratio [OR] = 3.35 [95% CI = 2.30–4.90]), ≥ 60 years old (OR = 5.80 [3.63–9.27]), overweight (OR = 4.17 [2.77–6.29]), and obese (OR = 8.82 [5.56–13.98]) were more likely to have MS. The study population experienced high cardiometabolic risk, requiring government efforts to control MS and related risk factors, especially obesity.

Mitochondrial uncoupling proteins regulate angiotensin-converting enzyme expression: crosstalk between cellular and endocrine metabolic regulators suggested by RNA interference and genetic studies.

Uncoupling proteins (UCPs) regulate mitochondrial function, and thus cellular metabolism. Angiotensin-converting enzyme (ACE) is the central component of endocrine and local tissue renin-angiotensin systems (RAS), which also regulate diverse aspects of whole-body metabolism and mitochondrial function (partly through altering mitochondrial UCP expression). We show that ACE expression also appears to be regulated by mitochondrial UCPs. In genetic analysis of two unrelated populations (healthy young UK men and Scandinavian diabetic patients) serum ACE (sACE) activity was significantly higher amongst UCP3-55C (rather than T) and UCP2 I (rather than D) allele carriers. RNA interference against UCP2 in human umbilical vein endothelial cells reduced UCP2 mRNA sixfold (P < 0·01) whilst increasing ACE expression within a physiological range (<1·8-fold at 48 h; P < 0·01). Our findings suggest novel hypotheses. Firstly, cellular feedback regulation may occur between UCPs and ACE. Secondly, cellular UCP regulation of sACE suggests a novel means of crosstalk between (and mutual regulation of) cellular and endocrine metabolism. This might partly explain the reduced risk of developing diabetes and metabolic syndrome with RAS antagonists and offer insight into the origins of cardiovascular disease in which UCPs and ACE both play a role.

Retinal vascular imaging in early life: insights into processes and risk of cardiovascular disease.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality globally. In recent years, studies have shown that the origins of CVD may be traced to vascular and metabolic processes in early life. Retinal vascular imaging is a new technology that allows detailed non-invasive in vivo assessment and monitoring of the microvasculature. In this systematic review, we described the application of retinal vascular imaging in children and adolescents, and we examined the use of retinal vascular imaging in understanding CVD risk in early life. We reviewed all publications with quantitative retinal vascular assessment in two databases: PubMed and Scopus. Early life CVD risk factors were classified into four groups: birth risk factors, environmental risk factors, systemic risk factors and conditions linked to future CVD development. Retinal vascular changes were associated with lower birth weight, shorter gestational age, low-fibre and high-sugar diet, lesser physical activity, parental hypertension history, childhood hypertension, childhood overweight/obesity, childhood depression/anxiety and childhood type 1 diabetes mellitus. In summary, there is increasing evidence supporting the view that structural changes in the retinal microvasculature are associated with CVD risk factors in early life. Thus, the retina is a useful site for pre-clinical assessment of microvascular processes that may underlie the future development of CVD in adulthood.

Mitochondrial uncoupling proteins regulate angiotensin-converting enzyme expression: crosstalk between cellular and endocrine metabolic regulators suggested by RNA interference and genetic studies.

Uncoupling proteins (UCPs) regulate mitochondrial function, and thus cellular metabolism. Angiotensin‐converting enzyme (ACE) is the central component of endocrine and local tissue renin–angiotensin systems (RAS), which also regulate diverse aspects of whole‐body metabolism and mitochondrial function (partly through altering mitochondrial UCP expression). We show that ACE expression also appears to be regulated by mitochondrial UCPs. In genetic analysis of two unrelated populations (healthy young UK men and Scandinavian diabetic patients) serum ACE (sACE) activity was significantly higher amongst UCP3‐55C (rather than T) and UCP2 I (rather than D) allele carriers. RNA interference against UCP2 in human umbilical vein endothelial cells reduced UCP2 mRNA sixfold (P < 0·01) whilst increasing ACE expression within a physiological range (<1·8‐fold at 48 h; P < 0·01). Our findings suggest novel hypotheses. Firstly, cellular feedback regulation may occur between UCPs and ACE. Secondly, cellular UCP regulation of sACE suggests a novel means of crosstalk between (and mutual regulation of) cellular and endocrine metabolism. This might partly explain the reduced risk of developing diabetes and metabolic syndrome with RAS antagonists and offer insight into the origins of cardiovascular disease in which UCPs and ACE both play a role.

An Optimized and Simplified System of Mouse Embryonic Stem Cell Cardiac Differentiation for the Assessment of Differentiation Modifiers

Generating cardiomyocytes from embryonic stem cells is an important technique for understanding cardiovascular development, the origins of cardiovascular diseases and also for providing potential reagents for cardiac repair. Numerous methods have been published but often are technically challenging, complex, and are not easily adapted to assessment of specific gene contributions to cardiac myocyte differentiation. Here we report the development of an optimized protocol to induce the differentiation of mouse embryonic stem cells to cardiac myocytes that is simplified and easily adapted for genetic studies. Specifically, we made four critical findings that distinguish our protocol: 1) mouse embryonic stem cells cultured in media containing CHIR99021 and PD0325901 to maintain pluripotency will efficiently form embryoid bodies containing precardiac mesoderm when cultured in these factors at a reduced dosage, 2) low serum conditions promote cardiomyocyte differentiation and can be used in place of commercially prepared StemPro nutrient supplement, 3) the Wnt inhibitor Dkk-1 is dispensable for efficient cardiac differentiation and 4) tracking differentiation efficiency may be done with surface expression of PDGFRα alone. In addition, cardiac mesodermal precursors generated by this system can undergo lentiviral infection to manipulate the expression of specific target molecules to assess effects on cardiac myocyte differentiation and maturation. Using this approach, we assessed the effects of CHF1/Hey2 on cardiac myocyte differentiation, using both gain and loss of function. Overexpression of CHF1/Hey2 at the cardiac mesoderm stage had no apparent effect on cardiac differentiation, while knockdown of CHF1/Hey2 resulted in increased expression of atrial natriuretic factor and connexin 43, suggesting an alteration in the phenotype of the cardiomyocytes. In summary we have generated a detailed and simplified protocol for generating cardiomyocytes from mES cells that is optimized for investigating factors that affect cardiac differentiation.

OP01.04: IUGR twin fetuses and aorta intima media thickness: a twin model to study the origin of cardiovascular disease

OP01.04: IUGR twin fetuses and aorta intima media thickness: a twin model to study the origin of cardiovascular disease

UP TO DATE STATINS IN PRIMARY AND SECONDARY PREVENTION OF CARDIOVASCULAR DISEASES

Early and aggressive treatment of patients with risk factors and clinically manifest cardiovascular diseases is one of the priorities of modern medicine. This therapy usually consists of several components according to multifactor origin of cardiovascular disease (CVD). Correction of lipid metabolism has become one of the strategic directions. First-line agents in the treatment of dyslipidemia in patients with CVD risk factors, of course, are statins. The results of multi-center studies showing the benefits of rosuvastatin in the prevention and treatment of cardiovascular diseases are presented.

Developmental Origins of Adult Disease: Part 1: Cardiovascular Disease

There is now considerable evidence from numerous epidemiologic, animal, and clinical studies demonstrating the association of early life conditions and increased risk of subsequent adult disease such as cardiovascular, renal, and metabolic disease. This first of three articles reviews the developmental origins of cardiovascular disease and the proposed underlying mechanisms.

Early Origins of Cardiovascular Disease in Pediatric Chronic Kidney Disease

The importance of cardiovascular disease in adults with chronic kidney disease is now well recognized. For children who develop chronic kidney disease, cardiovascular disease is also a leading cause of eventual morbidity and mortality. Although the clinical manifestations of cardiovascular disease may not be apparent until later, early subclinical findings can be observed even during childhood. This review updates the reader on the epidemiology of cardiovascular disease in pediatric chronic kidney disease, discusses risk factors and potential mechanisms of accelerated cardiovascular disease, reviews evidence of early manifestations of cardiovascular disease in pediatric chronic kidney disease, and briefly discusses prevention and treatment strategies.

Developmental Origins of Cardiovascular Disease

Developmental Origins of Cardiovascular Disease

Altered regional blood flow in the fetus: the origins of cardiovascular disease?

A fetal response to hypoxia and other adverse influences is to redistribute blood flow in order to "spare" the brain. This, however, is associated with reduced growth of the liver and kidneys. The long-term consequences of fetal redistribution of blood flow are unknown, but preliminary evidence suggests that there is an increased risk of coronary heart disease and hypertension in later life.