Early Development Of Cardiovascular Disease Research Articles

Searching for new genes associated with the familial hypercholesterolemia phenotype using whole-genome sequencing and machine learning.

One of the most common congenital metabolic disorders is familial hypercholesterolemia. Familial hypercholesterolemia is a condition caused by a type of genetic defect leading to a decreased rate of removal of low-density lipoproteins from the bloodstream and a pronounced increase in the blood level of total cholesterol. This disease leads to the early development of cardiovascular diseases of atherosclerotic etiology. Familial hypercholesterolemia is a monogenic disease that is predominantly autosomal dominant. Rare pathogenic variants in the LDLR gene are present in 75-85 % of cases with an identified molecular genetic cause of the disease, and variants in other genes (APOB, PCSK9, LDLRAP1, ABCG5, ABCG8, and others) occur at a frequency of < 5 % in this group of patients. A negative result of genetic screening for pathogenic variants in genes of the low-density lipoprotein receptor and its ligands does not rule out a diagnosis of familial hypercholesterolemia. In 20-40 % of cases, molecular genetic testing fails to detect changes in the above genes. The aim of this work was to search for new genes associated with the familial hypercholesterolemia phenotype by modern high-tech methods of sequencing and machine learning. On the basis of a group of patients with familial hypercholesterolemia (enrolled according to the Dutch Lipid Clinic Network Criteria and including cases confirmed by molecular genetic analysis), decision trees were constructed, which made it possible to identify cases in the study population that require additional molecular genetic analysis. Five probands were identified as having the severest familial hypercholesterolemia without pathogenic variants in the studied genes and were analyzed by whole-genome sequencing on the HiSeq 1500 platform (Illumina). The whole-genome sequencing revealed rare variants in three out of five analyzed patients: a heterozygous variant (rs760657350) located in a splicing acceptor site in the PLD1 gene (c.2430-1G>A), a previously undescribed single-nucleotide deletion in the SIDT1 gene [c.2426del (p.Leu809CysfsTer2)], new missense variant c.10313C>G (p.Pro3438Arg) in the LRP1B gene, and single-nucleotide deletion variant rs753876598 [c.165del (p.Ser56AlafsTer11)] in the CETP gene. All these variants were found for the first time in patients with a clinical diagnosis of familial hypercholesterolemia. Variants were identified that may influence the formation of the familial hypercholesterolemia phenotype.

The NGS panel for genetic testing in cardiology: from the evaluation of disease risk to pharmacogenetics

Cardiovascular diseases (CVD) are a leading cause of mortality in many countries worldwide. Genetic testing is an integral part of CVD prevention. The most common hereditary diseases in the practice of a cardiologist are cardiomyopathy and channelopathy (arrhythmogenic syndromes), as well as familial hypercholesterolemia, which causes a high risk of atherosclerosis and coronary heart disease (CHD). The total carrier frequency of pathogenic variants is 1:100. Timely genetic diagnosis is necessary for conditions that can lead to sudden cardiac death (for example, long QT syndrome, Brugada syndrome, arrhythmogenic cardiomyopathies). Pharmacogenetic testing is also important in cardiology, since it allows taking into account the role of genetic factors in the formation of a response to therapy. Incorporating individual patient characteristics can increase efficiency and minimize the likelihood of complications. The design of modern targeted cardiopanels must necessarily take into account monogenic and oligogenic forms of dyslipidemia and cardiovascular pathologies, polymorphic markers associated with a violation of the lipid spectrum of blood plasma and the early development of CVD in a particular population, as well as a minimum set of pharmacogenetic markers according to modern recommendations for clinical pharmacologists. In this review we provide a justification for the optimal design of such a panel for use in medical practice and scientific research.

Air Pollution, Built Environment, and Early Cardiovascular Disease.

As the world's population becomes increasingly urbanized, there is growing concern about the impact of urban environments on cardiovascular health. Urban residents are exposed to a variety of adverse environmental exposures throughout their lives, including air pollution, built environment, and lack of green space, which may contribute to the development of early cardiovascular disease and related risk factors. While epidemiological studies have examined the role of a few environmental factors with early cardiovascular disease, the relationship with the broader environment remains poorly defined. In this article, we provide a brief overview of studies that have examined the impact of the environment including the built physical environment, discuss current challenges in the field, and suggest potential directions for future research. Additionally, we highlight the clinical implications of these findings and propose multilevel interventions to promote cardiovascular health among children and young adults.

Familial Hypercholesterolemia and Its Current Diagnostics and Treatment Possibilities: A Literature Analysis.

Familial hypercholesterolemia (FH) is a common, inherited disorder of cholesterol metabolism. This pathology is usually an autosomal dominant disorder and is caused by inherited mutations in the APOB, LDLR, and PCSK9 genes. Patients can have a homozygous or a heterozygous genotype, which determines the severity of the disease and the onset age of cardiovascular disease (CVD) manifestations. The incidence of heterozygous FH is 1: 200-250, whereas that of homozygous FH is 1: 100.000-160.000. Unfortunately, FH is often diagnosed too late and after the occurrence of a major coronary event. FH may be suspected in patients with elevated blood low-density lipoprotein cholesterol (LDL-C) levels. Moreover, there are other criteria that help to diagnose FH. For instance, the Dutch Lipid Clinical Criteria are a helpful diagnostic tool that is used to diagnose FH. FH often leads to the development of early cardiovascular disease and increases the risk of sudden cardiac death. Therefore, early diagnosis and treatment of this disease is very important. Statins, ezetimibe, bile acid sequestrants, niacin, PCSK9 inhibitors (evolocumab and alirocumab), small-interfering-RNA-based therapeutics (inclisiran), lomitapide, mipomersen, and LDL apheresis are several of the available treatment possibilities that lower LDL-C levels. It is important to say that the timeous lowering of LDL-C levels can reduce the risk of cardiovascular events and mortality in patients with FH. Therefore, it is essential to increase awareness of FH in order to reduce the burden of acute coronary syndrome (ACS).

Systemic consequences of abnormal cholesterol handling: Interdependent pathways of inflammation and dyslipidemia.

Metabolic conditions such as obesity and associated comorbidities are increasing in prevalence worldwide. In chronically inflamed pathologies, metabolic conditions are linked to early onset cardiovascular disease, which remains the leading cause of death despite decades of research. In recent years, studies focused on the interdependent pathways connecting metabolism and the immune response have highlighted that dysregulated cholesterol trafficking instigates an overactive, systemic inflammatory response, thereby perpetuating early development of cardiovascular disease. In this review, we will discuss the overlapping pathways connecting cholesterol trafficking with innate immunity and present evidence that cholesterol accumulation in the bone marrow may drive systemic inflammation in chronically inflamed pathologies. Lastly, we will review the current therapeutic strategies that target both inflammation and cholesterol transport, and how biologic therapy restores lipoprotein function and mitigates the immune response.

Chronic diseases of adults programmed in childhood

The conditions of human development during the stages of early ontogenesis are of great importance for human health throughout the rest of his life. The period of intrauterine development and childhood are vulnerable stages of organism formation, when metabolic processes have the greatest plasticity and can be subject to deformation. Exposure to a number of external factors during this period of time can have a significant impact on the functional activity of genes controlling neurotransmission, immune response, endocrine functions and, thus, program the spectrum of metabolic disorders that can lead later to the formation of chronic diseases: obesity, type 2 diabetes, atherosclerosis and diseases of cardiovascular system. Negative programming influence on the metabolic profile and cardiovascular risk is caused by such factors as maternal obesity, complicated pregnancy and childbirth, prematurity, early separation from the mother, violation of child feeding in the 1st year of life. The risk of early development of cardiovascular disease, metabolic syndrome, obesity and diabetes mellitus is significantly increased in individuals who have experienced traumatic stressors during childhood associated with economic disadvantage of the family, parental divorce, neglect, abuse, parental neglect, sexual violence, death of parents, family members, close friends, bullying in the children's community. An in-depth study of this problem, along with the development and organization of measures for monitoring and prevention, in the long term can reduce the burden of chronic non-infectious diseases, improve quality of life, reduce disability, incapacitation and mortality in the adult population..

Glycoprotein Acetyls: A Novel Inflammatory Biomarker of Early Cardiovascular Risk in the Young.

BackgroundLow‐grade inflammation in the young may contribute to the early development of cardiovascular disease. We assessed whether circulating levels of glycoprotein acetyls (GlycA) were better able to predict the development of adverse cardiovascular disease risk profiles compared with the more commonly used biomarker high‐sensitivity CRP (C‐reactive protein).Methods and ResultsA total of 3306 adolescents and young adults from the Avon Longitudinal Study of Parents and Children (mean age, 15.4±0.3; n=1750) and Cardiovascular Risk in Young Finns Study (mean age, 32.1±5.0; n=1556) were included. Baseline associations between inflammatory biomarkers, body composition, cardiovascular risk factors, and subclinical measures of vascular dysfunction were assessed cross‐sectionally in both cohorts. Prospective risk of developing hypertension and metabolic syndrome during 9‐to‐10‐year follow‐up were also assessed as surrogate markers for future cardiovascular risk. GlycA showed greater within‐subject correlation over 9‐to‐10‐year follow‐up in both cohorts compared with CRP, particularly in the younger adolescent group (r=0.36 versus 0.07). In multivariable analyses, GlycA was found to associate with multiple lifestyle‐related cardiovascular disease risk factors, cardiometabolic risk factor burden, and vascular dysfunction (eg, mean difference in flow‐mediated dilation=−1.2 [−1.8, −0.7]% per z‐score increase). In contrast, CRP levels appeared predominantly driven by body mass index and showed little relationship to any measured cardiovascular risk factors or phenotypes. In both cohorts, only GlycA predicted future risk of both hypertension (risk ratio [RR], ≈1.1 per z‐score increase for both cohorts) and metabolic syndrome (RR, ≈1.2–1.3 per z‐score increase for both cohorts) in 9‐to‐10‐year follow‐up.ConclusionsLow‐grade inflammation captured by the novel biomarker GlycA is associated with adverse cardiovascular risk profiles from as early as adolescence and predicts future risk of hypertension and metabolic syndrome in up to 10‐year follow‐up. GlycA is a stable inflammatory biomarker which may capture distinct sources of inflammation in the young and may provide a more sensitive measure than CRP for detecting early cardiovascular risk.

Management of Hypertension in Elderly Pregnant Women with IVF Conception: A Case Report

Introduction: Hypertensive complications associated with pregnancy are the primary cause of maternal and fetal morbidity. Early development of cardiovascular disease is also anticipated relatively early after pregnancy is terminated. Over the past 20 years, infertility treatments have steadily increased and proven effective in achieving significant successful conception rates and live birth rates, even among women younger than 35 years of age.&#x0D; Symptoms and important clinical findings: A 45 year sold female was admitted in AVBRH on date 22/01/2021 with chief complaint of breathing difficulty (elderly G5P1D1A3 with 28 weeks of gestational age)having history of previous LSCS with IVF conception with gestational hypertension.&#x0D; Obstetric history: Patient had bad obstetric history of three abortionsand one still-birth. In 2017 she had got the menopause. After menopause she took the treatment in AVBRH Sawangi (M) Wardha and got the regular menses.After regular menses, shereceived IVF cycle and she was conceived in 2nd IVF cycle.&#x0D; The main diagnoses, therapeutic interventions, and outcomes: After physical examination and investigations, this case was diagnosed having 28 weeks of gestation with hypertension. Patient had previous history of LSCS.Patient was treated with antihypertensive drugs to reduce the symptoms of eclampsia. Alsoshe was provided calcium supplement and iron supplement. Present case was stable but ultrasonography revealedsign of stage I- intra uterine growth restriction.&#x0D; Nursing perspectives: Fluid replacement i.e. DNS and RL, monitoring offetal heart rate and vital signs per hourly.&#x0D; Conclusion: Conception with in vitro fertilization have increased risk of gestational hypertension as well as fetal complications like intra uterine growth restriction. But timely treatment and management improves the outcome of pregnancy.

Ambient air pollution and cardiovascular disease in Ugandan adolescents with perinatally acquired HIV: a cross-sectional study

BackgroundAir pollution is known to induce systemic inflammation and contribute to cardiovascular disease. The effects of ambient air pollution on adolescents living with perinatally acquired HIV (PHIV) in Africa has been understudied. In this study, we aim to investigate the relationship between particulate matter, a common proxy indicator for air pollution, and markers of inflammation, monocyte activation, and cardiovascular disease risk. MethodsWe recruited a cohort of PHIV-positive and HIV-negative adolescents who were from around Kampala, aged 10–18 years, had no known active infections, and who lived within 40 km of an PM2·5 monitoring site. Adolescents with PHIV were on ART with HIV-1 RNA concentrations ≤400 copies/mL. Daily ambient concentrations of particulate matter (PM2·5), a proxy for air pollution, were measured with continuous central site monitoring using a Beta Attenuation Monitor or E-Samplers from the GeoHealth Hub. We measured carotid intima media thickness (IMT) using ultrasound, plasma concentrations of soluble CD14 and CD163 as markers of monocyte activation, plasma markers of systemic inflammation (hsCRP, IL6, sTNFRI), oxidised lipids, and intestinal permeability (zonulin). FindingsOne hundred and nineteen participants were included (69 with PHIV, 50 were HIV-negative). Median age was 12·7 years (IQR 11·4–14·2) years, 55% were female and 63% lived below the extreme poverty line (living with <US$1·90 a day). Median CD4+ cell count was 962 cells/μL (643–1313), 82% had viral load <20 copies/mL and median ART duration was 12·1 years (9·7–13·3) years. Overall median daily PM2·5 exposure was 29·08 μg/m3 (23·40–41·70), considered a moderate health risk (WHO definition). There was no significant difference in exposure of PM2·5 between groups (p=0·073), nor between sexes (p=0·099). PM2·5 concentrations significantly correlated with intestinal permeability (zonulin; r=0·43, p<0·001), monocyte activation (soluble CD163: r=0·25, p=0·053), and IMT (r=0·35, p=0·004) in participants with PHIV but not in those who were HIV-negative (p≥0·05 for all three correlations in HIV-negative children). In multivariable quantile regression models, after adjusting for age, sex, and, separately, soluble CD163 and zonulin, daily PM2·5 concentrations remained associated with IMT (β=0·005, 95%CI [0·001–0·009], p=0·007 and β=0·004, 95%CI [0·001–0·008], p=0·014, respectively) in children with PHIV. InterpretationPM2·5 exposure was associated with elevated subclinical vascular disease in adolescents with PHIV but not HIV-negative adolescents, despite there being no significant difference in exposure between these two groups. Our findings suggest the combined effects of HIV infection and air pollution may amplify and contribute to early development of cardiovascular disease. FundingNICHD K23HD088295 (SDF); University Hospitals Cleveland Medical Center; The Clinical and Translational Science Collaborative of Cleveland; and UL1TR002548 from the National Center for Advancing Translational Sciences.

Prevalence of low high-density lipoprotein among young adults receiving antiretroviral therapy in Zambia: An opportunity to consider non-communicable diseases in resource-limited settings.

BackgroundWith the introduction of effective antiretroviral therapy (ART), people living with HIV (PLWH) are surviving longer and are at risk for developing metabolic abnormalities that contribute to cardiovascular disease (CVD). In Sub-Saharan Africa (SSA), there is a paucity of epidemiological data on lipid profiles among young adults receiving ART. This study aimed to estimate the prevalence of low high-density lipoprotein cholesterol (HDL-c), a cardioprotective lipid class, and whether it differed by age among adults on ART in Livingstone, Zambia.MethodsFrom April to December 2019, we conducted a cross-sectional study of 597 PLWH [n = 58 aged 18–24 years (young adults); n = 539 aged ≥25 years (adults)] on ART for ≥6 months. Data collected included demographic and lifestyle information, anthropometrics, viral load (VL), CD4 count, blood pressure, lipid profiles and fasting/random blood glucose. Clinical measures were defined as: low HDL-c [<1.0 mmol/L for men, <1.3 for women], increased waist circumference (WC) [≥94 cm for men, ≥80 cm for women], high triglycerides (TG) [≥1.7 mmol/l], and virological failure (VF) [VL ≥1000 copies/μl]. We used logistic regression to examine the association between age and low HDL-c after adjusting for multiple variables.ResultsAmong the young adults, 60% (35/58) were women, median (25th, 75th percentile) age 21 years (18, 23), and median time on ART 116 months (60, 144). Among adults, 63% (342/539) were women, median age 46 years (40, 53) and median time on ART 108 months (60, 144). Young adults had a lower CD4 count compared to adults (median, 492 vs. 568 cells/μL, p = 0.010) and higher prevalence of VF (29% vs. 17%, p = 0.016). In young adults, prevalence of low HDL-c was significantly higher than in adults (63 vs. 38%, p<0.001). A high proportion of young adults (75%) and adults (58%) with low HDL-c were on dolutegravir (DTG)-based ART regimens. After adjusting for sex, duration on ART, WC, body mass index, ART regimen, VF, CD4 count, low density lipoprotein cholesterol, blood pressure and smoking, young adults were significantly more likely than adults to have low HDL-c (odds ratio 2.93; 95% confidence interval 1.46–5.86).ConclusionLow HDL-c is highly prevalent among young adult with HIV in SSA independent of other risk factors for metabolic derangements. Lipid abnormalities among young PLWH may contribute to the early development of cardiovascular diseases in this population. This highlights the need to consider low HDL-c in the quest to reduce CVD risk among young adults on ART in SSA.

Traditional cardiovascular risk factors and glomerular filtration rate in patients with rheumatoid arthritis

Abstract The leading cause of premature death in rheumatoid arthritis (RA) is cardiovascular complications associated with vascular atherosclerosis. Even a slight decrease in glomerular filtration rate (GFR) is an important independent risk factor for cardiovascular complications. The purpose of the study: to determine GFR in patients with RA, to identify the relationship between GFR and traditional risk factors for the development of cardiovascular complications. Methods The study included 58 patients with RA aged 21 to 60 years, who do not have concomitant kidney diseases, arterial hypertension (AH) of stage III, and diseases accompanied by the development of secondary nephropathy. GFR was calculated using the CKD-EPI formula. All patients were evaluated for traditional cardiovascular risk factors: hypertension, dyslipidemia, a complicated hereditary history of early development of cardiovascular diseases, overweight, and smoking. The European SCORE scale and the Reynolds Risk Score (RRS) predictive scale in the EULAR modification were used to assess the total risk of cardiovascular complications. Results Women predominated among the patients – 61 (86.6%). The mean age of patients is 45 years. Seropositive patients with rheumatoid factor prevailed, with moderate and high activity of the process, III x-ray stage according to Steinbroker. In 36 (62%) patients, GFR was in the range from 60 to 89 ml/min/1.73m2, in 38% of patients-more than 90 ml/min/1,73m2. The average GFR in patients with RA was 88.43±16.13 ml/min/1.73m2, in the comparison group-83.54±15.22 ml/min/1.73m2 (p=0.063). Arterial hypertension was diagnosed in 40 (68.9%) patients with RA: 70.2% of women and 55.3% of men. The level of total cholesterol in patients with RA is significantly higher than in the comparison group (p&amp;lt;0.001), even in patients younger than 40 years, the level of total cholesterol is higher than in those without arthritis (5±1.15 and 4.14±0.21 mmol/l, p=0.027). The average value of the SCORE scale in RA patients and in the comparison group is generally comparable, and when compared by age periods. In patients younger than 40 years who suffer from hypertension, GFR is lower than in patients of the same age, but without hypertension: 86 [79; 101.5] and 104.5 [101; 112] ml/min/1.73m2, respectively, p=0.043. Relationships between GFR and traditional cardiovascular risk factors were identified: body mass index (r=−0.414; p&amp;lt;0.001), total cholesterol levels (r=−0.402; p&amp;lt;0.001), low-density lipoproteins (r=−0.331; p=0.013), triglycerides (r=−0.283, p=0.028), systolic BP (r=−0.257; p=0.027), diastolic BP (r=−0.255; p=0.029) at the time of the study, the value of the Score scale (r=−0.529; p&amp;lt;0.001) and RRS (r=−0.341; p=0.031). Conclusion Most patients with rheumatoid arthritis showed a decrease in glomerular filtration rate, and GFR is associated with traditional risk factors for cardiovascular events. Funding Acknowledgement Type of funding source: None

Hypertension in children and adolescents

Hypertension is a major health problem in most developed and developing countries. Worldwide, approximately 1 billion people have hypertension, and 13% of all deaths are closely related to hypertension. Recently, the prevalence of elevated blood pressure (BP) in children and adolescents has increased, probably due to the increased prevalence of overweight and obesity among youths. Increasing evidence suggests that adult hypertension has its antecedents in childhood, as childhood BP predicts adult BP. Additionally, pediatric hypertension may cause premature atherosclerosis and early development of cardiovascular disease. Therefore, the identification and treatment of hypertension in childhood is likely to have an important impact on long-term outcomes of cardiovascular disease. International hypertension guidelines for children and adolescents have recently been significantly revised, especially regarding the diagnosis of hypertension. This review presents the recent guidelines for the diagnosis, evaluation, management, and treatment of hypertension in children and adolescents.

Impaired Cardiovascular Responses To Acute Exercise In Adults With Cerebral Palsy

Cerebral palsy (CP) is a non-progressive and permanent neurological disorder leading to musculoskeletal dysfunction and immobility. A major clinical problem with CP is early development of cardiovascular diseases with increased rates of mortality. Due to the inevitability of motor dysfunction adults with CP can develop health risk factors, such as obesity and hypertension, at a higher rate compared to the general population. To date, the physiological basis for CP has not been established; how cardiovascular dynamics, such as heart rate (HR), blood pressure (BP), and blood flow (BF), are controlled in individuals with CP has never been identified. PURPOSE: To determine differential cardiovascular responses to acute dynamic exercise in adults with CP. METHODS: Total of ten adults with and without CP participated in the study. HR from ECG, beat-to-beat arterial BP from Finapres and brachial BP, and respiration via pneumobelt were continuously measured before, during and after 2 minutes of dynamic handgrip exercise at 35% and 50% of maximal voluntary contraction. In addition, diameter, blood velocity, and flow of the brachial artery were measured using Doppler ultrasound on the contracting arm throughout the experiment. RESULTS: HR was significantly increased to exercise from rest in both groups with no group differences (∆9.8±1.2 control vs. ∆10.1±8.4 CP, bpm). Both control and CP groups had increases in BF during exercise compared to at rest (∆132±22 control vs. ∆75±32 CP, ml/min). Mean BP was significantly increased to exercise from rest in control; however, there were only minor changes in BP to exercise from rest in CP group (∆7.2±1.6 control, ∆2.2±0.1 CP, mmHg). CONCLUSION: While HR and BF increased to exercise from rest in similar fashion, BP did not change to exercise in adults with CP. Our preliminary data speculate that other mechanisms, possibly vascular contribution from non-contracting limbs, may contribute to impaired BP response during exercise in CP. Supported by CASA RSCA Infusion, Central RSCA, and Undergraduate Research Grant, SJSU

Patients with Premature Cardiovascular Diseases in Ambulatory Practice: Demographic Characteristics, Risk Factors and Adherence to the Medical Therapy (Data of RECVASA Registry)

Aim . To evaluate the gender characteristics, educational level, cardiovascular diseases (CVD) risk factors and adherence to drug treatment in patients with premature CVD in an outpatient prospective registerу. Material and methods . 3690 patients with hypertension, coronary artery disease, chronic heart failure, atrial fibrillation and their combinations were enrolled in the RECVASA registry in Ryazan region of Russia. Groups of patients with early development of CVD (criterion 1 – the age of 18-49 years old, criterion 2 – the age of men 18-54 years old and women – 18-64 years old) were compared with the corresponding older groups. The gender characteristics, educational level, CVD risk factors, and adherence to drug treatment were analyzed. Results . According to criterion 1, the age groups of 18-49 years old and ≥50 years old included 347 (9.4%) and 3343 (90.6%) patients, respectively, 144 (41.5%) and 902 (27, 0%), respectively were men, p 5 mmol/L) was diagnosed significantly less frequently in patients with early development of CVD than in the older age group (47.8 vs 54.6%; p=0.047); these differences were obtained due to women (46.9 vs 58.8%; p=0.008), the proportion of individuals with hypercholesterolemia did not significantly differ among men. According to criterion 2, statistically significant differences in the frequency of hypercholesterolemia were not detected among both men and women. There was no differences in the incidence of family history (FH) of premature CVD in the study groups, while the proportion of patients with FH of premature CVD was significantly higher in men <55 years old than in women <65 years old (44.8 vs 37.7%; p<0.0001). According to criterion 1 the proportion of patients with low adherence to treatment was higher in patients with early development of CVD than in the older age group (57.1% vs 46.1%; p=0.0006), the proportion of patients with high adherence was 22.9% and 32.4% (p=0.0013), respectively. According to criterion 2, there were no differences in adherence to treatment. Conclusions . According to RECVASA registry, patients with early development of CVD were more likely to be men, in accordance with criterion 1. Patients with early development of CVD, including men and women, according to both criteria, were characterized by a significantly higher proportion of individuals with higher education and a higher proportion of smokers. In patients with early development of CVD using criterion 1, in contrast to criterion 2, hypercholesterolemia was diagnosed significantly less often than in the older age group. It is preferable to use criterion 1 to assess hypercholesterolemia in patients with early development of CVD. The proportion of individuals with FH of premature CVD was significantly higher in men <55 years old than in women <65 years old. Patients with early development of CVD according to criterion 1 were characterized by a lower adherence to drug treatment. Individuals with early development of CVD, especially <50 years old are the target group for comprehensive prevention, not only due to improving the quality of proven effective drug therapy, but also by correcting risk factors and increasing level of adherence to treatment.

Pentraxin 3 as a marker of endothelial dysfunction in young women with polycystic ovary syndrome (PCOS)

One of the consequences of polycystic ovary syndrome (PCOS) is an increased risk of early development of cardiovascular diseases. Pentraxin-3 (PTX-3) is a new potential marker of endothelial dysfunction. The aim of the study was to assess PTX3 and other markers of endothelial dysfunction in PCOS women. The study enrolled 99 stable body mass PCOS women (17 normal weight, 21 overweight and 61 obese). Anthropometric measurements and serum/plasma levels of glucose, insulin, lipids, estradiol, testosterone, sex hormone binding globulin, 17-OH progesterone, free androgen index, pentraxin-3 (PTX3), soluble intercellular (sICAM-1) and vascular cell adhesion molecule 1 (sVCAM-1), endothelin-1 and total nitric oxide metabolites (tNO) concentrations were assessed. Groups were divided into tercile-subgroups according to PTX3 serum levels. Serum PTX3 tercile-subgroups significantly differed in respect to tNO, endothelin-1 and sVCAM-1, but not sICAM-1. The levels of tNO, endothelin-1 and sVCAM-1 were significantly decreased in the subgroup with the lowest PTX3 levels compared to both middle (tNO and endothelin 1) and upper tercile subgroups (all of them). There were significant positive correlations between log10(PTX3) and log10(tNO) (r = 0.34, p < .001), log10(endothelin-1) (r = 0.41, p < .001) as well as sVCAM-1 levels (r = 0.22, p < .05). Circulating PTX-3 levels seem to be a marker of endothelial dysfunction in PCOS women.

Twelve Years Follow Up - Prevalence Trends Of Physical Inactivity And Overweight In Brazilian Adolescents

PURPOSE: Determine the physical inactivity and overweight prevalence in adolescents living at São Paulo State (Brazil) from 2005 to 2017. METHODS: We evaluated 3,845 adolescents as part of a cohort study that started in 2005 in São Paulo city. In this study we analyzed 2.012 both sex adolescents that were followed in 2005, 2009, 2013, 2015 and 2017. In 2005, adolescents were from 15 to 18 years of age. We assessed the habitual physical activity practice by International Physical Activity Questionnaire (IPAQ-short-8 version) considering active (AT) the adolescents that accumulated at least 300 minutes per week of moderate-vigorous PA and inactive (INA) if less than 300 min/week were reported. Body weight (kg) and height (m) were self-reported by questionnaire. BMI was calculated and the respective criteria for overweight classification were considered for Brazilian adolescents (CONDE and MONTEIRO, 2006). The anthropometry tendency changed overtime, and a linear regression model was designed to express the annual physical inactivity prevalence average and the excess of body weight. The significance was p<.05. RESULTS: In general, the prevalence of physical inactivity in 2005 was 50.4%, with significant increase to 53.2% (2009); 56.7% (2013); 59.2% (2015) and 60.2% (2017), with 0.91% annual increase. Higher variation was observed in girls than boys (1.32% x 0.89% per year). The overweight prevalence followed similar trend: 2005 (16.7%); 21.2% (2009); 25.8%); 28.2% (2013), 28.7% (2015) and 29.3% (2017) with 1.29% increase per year (p<.05). Girls presented significantly and higher percentage change than boys (1.56 vs. 1.15% per year). CONCLUSIONS: Data showed progressive trend of high physical inactivity and body fat increase, leading to an incidence of obesity in the next 10 years around 71.0% of all adolescents living in Sao Paulo State 37.2% of physically inactive behavior. These data suggests an early development of cardiovascular disease, with higher impact in girls than boys. Also data strongly suggest to effectiveness of public health policies towards the physical inactivity prevention and the excess of body mass among adolescents are related to unhealthy behaviors of eating, drinking and PA.

Differential Effect of Obesity on Muscular Strength in Adults with Cerebral Palsy

Cerebral palsy (CP) is a non-progressive and permanent neurological disorder that is characterized by muscular deterioration and atrophy. The major clinical problem with CP is early development of cardiovascular disease with increased rates of mortality. Due to the inevitability of motor dysfunction adults with CP can develop health risk factors such as obesity at a higher rate compared to the general population. Limited information is available to identify levels of obesity and its relation to muscular function in adults with CP. PURPOSE: To determine whether severity of obesity may affect muscular function and strength in adults with CP. METHODS: We studied total of sixteen adults with and without CP. Muscular strength (i.e., torque, work, and power) during knee extension and flexion was measured at 90, 150, and 210 °/sec in the lower extremity using Humac Norm Isokinetic Dynamometer. Maximal isometric forearm muscular strength was measured using a handgrip dynamometer. Body mass index (BMI), waist to hip ratio, and whole-body scan from Dual Energy X-Ray Absorptiometry were used to identify the levels of obesity. RESULTS: Compared to control, individuals with CP had similar BMI (26.8±3.0 CP vs. 22.9±1.0 control kg/m2; P>0.05), % body fat (35.2±4.5 CP vs. 28.4±3.7 control %; P>0.05), and % leg fat (40.7±4.3 CP vs. 30.5±4.1 control %; P>0.05). However, waist to hip ratio was significantly greater in CP (0.90±0.02 CP vs. 0.80±0.02 control; P<0.05); muscular strength was significantly lower in CP compared to control (e.g., knee extensor peak torque at 90°/sec; 25.9±8.1 CP vs. 72.5±12.2 control ft-lb; P<0.05). There was no relationship between BMI and extensor/flexor peak torque in both groups; however, there was a linear relationship between waist to hip ratio and extensor/flexor peak torque only in CP group (R2=0.34). A strong inverse relationship between % leg fat and extensor/flexor peak torque was observed in both groups (R2=0.79). CONCLUSION: These findings suggest that central obesity rather than BMI appeared to influence muscular strength in CP adults. In addition, less fat in the legs rather than the total body may contribute for higher leg muscular strength in adults with CP. Supported by Central RSCA and Undergraduate Research Grant, SJSU

The Association of Measures of the Micro- and Macro-Vasculature with Selenium and GPx Activity in a Young Bi-Ethnic Population: The African-PREDICT Study

Objective: Selenium plays an important physiological role as component for antioxidant selenoproteins such as glutathione peroxidase (GPx). Since oxidative stress contributes to hypertension development, it is likely that selenium deficiency may contribute to the burden of cardiovascular disease. To better understand the involvement of selenium and GPx in the early development of cardiovascular disease, we investigated in young, healthy black and white African men and women whether measures of the micro- and macrovasculature are related to selenium and GPx activity.Methods: In young adults (N = 394; aged 20–30 years) we determined serum selenium, GPx activity, microvascular measures (central retinal artery equivalent, central retinal vein equivalent, arteriolar-to-venular ratio [AVR], and estimated glomerular filtration rate [eGFR]), and macrovascular measures (pulse wave velocity, 24-hour pulse pressure [PP] and augmentation index [Aix]).Results: In multivariable-adjusted regression analyses, there were vasculoprotective associations between serum selenium and a microvascular measure (AVR [β = 0.23; p = 0.036]) in black African women and with a macrovascular measure (24-hour PP [β = −0.15; p = 0.048]) in white African women. In turn, GPx activity also showed a protective association with a microvascular measure (eGFR) in white African men (β = 0.23; p = 0.035), as well as with macrovascular measures (AIx, PP) in the black (β = −0.25; p = 0.027) and white African men (β = −0.22; p = 0.035), and black African women (β = −0.32; p = 0.001).Conclusions: Collectively the findings suggest a protective role for the micronutrient selenium and GPx on both the micro- and macrovasculature in a young, healthy bi-ethnic population.

Effects of Different Antihypertensive Drug Combinations on Blood Pressure and Arterial Stiffness.

Introduction:Hypertension is significantly contributing to global mortality and morbidity and has been identified as the most important modifiable risk factor for early development of cardiovascular diseases (CVD).Aim:The aim of this study was to investigate the efficacy of different combinations of antihypertensive therapy on blood pressure, arterial stiffness and peripheral resistance in patients with essential hypertension using the brachial oscillometric ambulatory blood pressure monitor.Methods:This study was designed as an observational, prospective, multi centric study conducted in eight primary care centers of the Health Center of Canton Sarajevo during the period of six months. The study included 655 participants, both genders, aged between 30 and 75, who were diagnosed with hypertension according to the ESC/ESH guidelines. Participants were divided into six treatment groups based on the hypertensive drug therapy they were using; lisinopril, losartan or valsartan alone or in combination with hydrochlorothiazide (A, B and C group respectively) or combination of lisinopril, losartan or valsartan with/without hydrochlorothiazide together with amlodipine (D, E and F respectively). The participants were monitored at baseline, after 3 and 6 months (1st and 2nd follow-up). Brachial oscillometric ambulatory blood pressure monitor was used for measuring systolic (SBP), diastolic (DBP), pulse pressure (PP), pulse wave velocity (PWV) and peripheral resistance (PR).Results:SBP, DPB, PP, and PWV significantly decreased from baseline to 2nd follow-up in all treatment groups. The mean reductions in SBP were from -11.7 (95%CI; 9.3- 14.1) to -23.2 (95%CI; 18.3-28.1) mmHg and DBP reductions varied from -5.5 (95%CI; 3.9- 7.1) to -13.4 (95%CI; 7.7-19.1) mmHg. PWV decreased in all treatment groups (from -3.3% to -8.2%). Treatment regiment was not associated with significant differences in SBP, DBP, PP or PWV reductions or their values measured at 2nd follow-up. Peripheral resistance significantly decreased only in group C (p=0.011), group D (p=0.009) and group F (p=0.027).Conclusion:These data suggest that lisinopril/lisinopril + hydrochlorothiazide, losartan/losartan + hydrochlorothiazide and valsartan/valsartan + hydrochlorothiazide alone or in combination with amlodipine are equally effective and well tolerated for the reduction of both systolic and diastolic blood pressure and improve arterial stiffness in patients with essential hypertension.

Unhealthy Lifestyle and Nutritional Habits Are Risk Factors for Cardiovascular Diseases Regardless of Professed Religion in University Students.

To date, few studies have evaluated the possible association between religion and nutritional habits, lifestyle and cardiovascular risk in the university population. This study identified differences in the eating habits of Christian and Muslim university students and determined a possible association between the impact of religion on their lifestyles and the parameters related to cardiovascular risk. A cross-sectional study was performed with a sample population of 257 students (22.4 ± 4.76 year) at the campus of the University of Granada in Melilla (Spain). An anthropometric evaluation and a dietary assessment were performed. Blood pressure was also measured. There was a higher prevalence of overweight (29.1%) among Christian university students. The prevalence of pre-hypertension was similar between Christians and Muslims (48.3%) but was higher among Christian males (74.5%). Christian students presented higher levels of visceral fat. Students of both religions ingested carbohydrates, saturated fatty acids and total cholesterol, proteins, sodium and alcohol in excess. Significant positive correlations were found between food energy, sweets, snacks, soft drinks and body mass index (BMI) in both sexes and between the consumption of sausages-fatty meats and the systolic blood pressure (SBP) and body adiposity index (BAI) variables. Muslim students were less likely to consume alcohol (odds ratio [OR] = 7.88, 95% confidence interval [CI] = 4.27, 14.54). Christian and Muslim students presented improvable lifestyles and intake patterns. The high intake of saturated fatty acids, total cholesterol, sodium and alcohol in Christian students could lead to the early development of cardiovascular disease.