Risk Factor For Development Of Cardiovascular Disease Research Articles

Epigenomic biomarkers of cardiometabolic disease: How far are we from daily practice?

Determining whether someone has cardiometabolic disease (CMD), especially in the early stages, can be complicated. Risk stratification ordinarily depends on an extended process relying on medical history that typically considers blood pressure, cholesterol, smoking and diabetes status. Physicians have long relied on these key patient characteristics to assess CMD risk. However, these widely used clinical assessments are often identified later in life and by definition, in those individuals with progressed disease. This is partly because the onset of CMD naturally occurs in adulthood, however, the underlying processes can occur much earlier in life, even in the absence of obvious symptoms. For one thing, the pathways towards pathology may exist for years before symptom onset. Thus, among other things, there are opportunities to provide doctors with better insights into future disease prediction especially in younger adults with diabetes. The rapid rise in CMD together with the increased rates of obesity and diabetes in this population only emphasises the importance of predictive molecular biomarkers. One notable aspect is that traditional risk scores, such as those based on cholesterol measurements, are frequently found to be within normal ranges in younger populations. At the same time, given the significant overlap in risk factors for cardiovascular disease (CVD) and diabetes, the unmet clinical need is for early biomarkers of CMD that may help improve risk assessment in younger adults. This editorial highlights advances in the use of polygenic risk scores and emerging utility of genetic biomarkers to define intermediate CMD phenotypes discussing new classification criteria involving DNA methylation of genes to improve risk assessment. CMD is the number one cause of mortality and accounts for 31% of all global deaths. CMD is also multifactorial, comprising cardiovascular disease (CVD) and diabetes that have significant overlap in risk factors and disease biology. Diabetes is arguably the strongest risk factor for CVD development. Accounting for almost 90% of diabetes cases worldwide, type 2 diabetes (T2D) affects about 527 million people. The global economic burden is estimated at 1.3 trillion USD annually and is close to 1.8% of global GDP [1]. Despite the progress in preventive and therapeutic measures of CVD, the increasing CMD rates only underscore the important need of molecular biomarkers for early detection [2]. Determining whether someone has CMD usually involves an extended diagnostic process that has become essential for risk stratification and disease prevention [3]. While the onset of CMD typically occurs in adulthood, disease development commences much earlier, and this has scientists questioning whether molecular biomarkers could improve current prognostic risk scores. Predicting which people with T2D are most likely to develop CVD remains a significant challenge despite the recent advances in genetic mapping.Graphical abstract

Increased cardiovascular disease risk among adolescents and young adults with gastric cancer.

Previous studies have investigated cardiovascular disease (CVD) risks in cancer patients, but there is limited knowledge concerning the CVD risk in adult and young adolescent (AYA) survivors of gastric cancer. This study aims to investigate the incidence of CVD in AYA gastric cancer survivors, analyzing it by treatment type and identifying associated risk factors. We conducted a retrospective cohort study using Korean National Health Insurance Service data collected from 2006 to 2019. Propensity score matching (1:3, caliper < 0.1) was performed using the variables age, sex, income, residential area, and presence of comorbidities, and we classified participants into gastric cancer (n = 6562) and non-cancer control (n = 19,678) groups. Cox regression models were used to calculate hazard ratios (HRs) for CVD incidence. The study assessed CVD incidence by cancer treatment and identified risk factors through multivariable Cox regression. During a median 6.5-year follow-up, AYA gastric cancer survivors consistently exhibited greater CVD incidence. Their risk of CVD was significantly elevated compared to that of controls (HR, 1.18; 95% confidence interval [CI] 1.05-1.33). In particular, deep vein thrombosis (HR, 3.93; 95% CI 3.06-14.67) and pulmonary embolism (HR, 6.58; 95% CI 3.06-14.67) risks were notably increased. Chemotherapy was associated with an increased risk of stroke, heart failure, atrial fibrillation, deep vein thrombosis, and pulmonary embolism. Hypertension (HR, 1.58; 95% CI 1.10-2.26) and dyslipidemia (HR, 1.46; 95% CI 1.06-2.20) emerged as risk factors for CVD development. This study reports elevated risks of CVD in AYA gastric cancer survivors and emphasizes the need for vigilant monitoring of CVD in this population.

The Influence of Rheumatoid Arthritis and Osteoarthritis on the Occurrence of Arterial Hypertension: An 8-Year Prospective Clinical Observational Cohort Study.

Rheumatoid arthritis (RA) increases the risk of cardiovascular mortality and morbidity, including a 50-60% increased risk of cardiovascular disease (CVD). Arterial hypertension (HT) is considered the major contributing risk factor for CVD development in RA patients. In this investigation, we compared the incidence and prevalence of HT between RA and osteoarthritis (OA) and the influence of HT on CVD development in CVD-naive patients in both groups. This was a prospective clinical cohort investigation with an 8-year follow-up period. A total of 201 participants, 124 with RA (investigation group) and 77 with OA (control group), without diagnosed CVD or symptomatic heart failure were included. After selection according to inclusion and exclusion criteria, both groups underwent initial and final visits, and the investigation group underwent annual visits to assess disease activity. Case report forms were completed for each visit. The obtained data were analyzed by a statistician. No difference in the incidence or prevalence of HT was found between the investigation and control groups. No difference in the prevalence of HT was reported between the study groups and age-standardized data from the general population. The investigation group had a higher incidence of CVD than the control group. RA participants with long-term remission had a marginally lower HT prevalence. Although previous studies reported a higher HT prevalence in RA than in OA and the general population, our findings did not support this. The RA group had a higher incidence of CVD, but it is possible that optimal disease control with long-term remission could reduce HT incidence and prevalence while also having beneficial effects on other cardiovascular risk factors (CV) and, consequently, CVD occurrence.

Impact of Hematopoietic Cell Transplantation on Cardiovascular Risk Factors and Insulin Sensitivity

The use of hematopoietic cell transplantation (HCT) for treating malignant conditions in children has increased over the past five decades, leading to a growing population of long-term survivors.This population of childhood HCT survivors faces increased risks of adverse medical effects due to cancer treatments, including adverse cardiovascular disease (CVD) risk factors such as metabolic syndrome, insulin resistance. but the impact of exposure to HCT preparative conditioning regimen has not been clearly delineated. These risk factors, including obesity, dyslipidemia, hypertension, and insulin resistance (IR), are significant contributors to premature cardiovascular disease and represent a leading cause of non-relapse deaths in childhood cancer and HCT survivors. This study aimed to assess the early development of CVD risk factors and their relationship to insulin resistance in a large population of pediatric and young adult HCT survivors of childhood hematologic malignancies. The study compared their cardiovascular risk profiles, insulin resistance (measured by euglycemic hyperinsulinemic clamp studies), and body composition (determined by dual X-ray absorptiometry - DXA) with a cohort of sibling controls. We enrolled 151 HCT recipients (26.36 ±0.90 years at study enrollment; time since HCT of 2.6-31.5 years) and 92 sibling controls to complete at cardiovascular risk assessment including insulin sensitivity by hyperinsulinemic euglycemic clamp, anthropometry, body composition by dual X-ray absorptiometry, blood pressure, and serum biomarkers. We used linear models to test for mean differences in all continuous outcomes between survivors and siblings, accounting for intra-family correlations with generalized estimating equations. Recipients of HCT were found to have lower insulin sensitivity and more likely to have adverse CVD risk factors in comparison to their healthy siblings. Significantly higher percent fat mass and visceral adipose tissue, and significantly lower lean body mass were noted in HCT recipients than sibling controls despite having a similar body mass index between the two groups. Total body irradiation in the conditioning regimen was one of the strongest factors associated with lower insulin sensitivity, dyslipidemia and abnormal body composition leading to sarcopenic obesity. This study reveals that pediatric and young adult HCT survivors are more insulin resistant and have a higher prevalence of adverse cardiovascular risk factors compared to sibling controls. The presence of cardiovascular risk factors at a relatively young age raises concerns about an escalating trajectory of cardiovascular disease in this population. Therefore, regular monitoring of HCT survivors for cardiometabolic risk factors and early intervention will be crucial for preventing cardiovascular-related complications in the future. The findings underscore the importance of survivorship care for pediatric and young adult HCT survivors, with a focus on managing cardiovascular risk factors and promoting a healthy lifestyle to mitigate long-term adverse effects. Early identification and targeted interventions can significantly improve the long-term health outcomes of this vulnerable population, reducing the burden of cardiovascular disease and related complications.

Clonal Hematopoiesis of Indeterminate Potential: Current Understanding and Future Directions.

This article summarizes the current knowledge about clonal hematopoiesis of indeterminate potential (CHIP), its association with cardiovascular disease (CVD), and other outcomes, pathogenesis, postulated mechanisms of various pathologies, current knowledge gaps, possible targets of intervention, and therapeutic implications. Recently, a common age-related hematological entity known as CHIP has been identified as the independent risk factor for CVD. CHIP is defined as the presence of clonally expanded blood cells involving leukemogenic mutations without the evidence of malignancy. CHIP is known to increase the inflammatory state which in turn is thought to be responsible for increased risk of CVD. Apart from CVD and malignancy, CHIP is also associated with pulmonary embolism, COPD, CKD, stroke, altered metabolism, obesity, liver disease, and increased all-cause mortality. At the same time surprisingly, CHIP is found to have positive outcomes in bone marrow transplant patients and similar reciprocal association with Alzheimer's disease. The risk of CVD and cancer increases with the advancing age, and these two are the leading causes of death in the USA. CHIP is an independent risk factor for CVD development. Most patients with CHIP have somatic clonal mutations in epigenetic regulators, DNA repair genes, or regulatory tyrosine kinases without evidence of overt hematological malignancy. CHIP portends increased risk for leukemia development and carries twofold increased risk of CVD including CAD, MI, and poor prognosis in heart failure. CHIP is associated with various other pathologies making CHIP an area of active research interest in recent years. Current research efforts aim to bridge many knowledge gaps in understanding of CHIP that still exist.

Gallbladder disease is associated with the risk of cardiovascular disease among Uyghurs in Xinjiang: a prospective cohort study

BackgroundGallbladder disease (GBD) can increase the risk of cardiovascular disease (CVD). However, GBD has rarely been reported in the less developed, rural areas of Xinjiang. This study aimed to determine the prevalence of GBD and incidence of CVD in a prospective cohort study in rural Xinjiang. Moreover, the study aimed to explore the association between GBD and CVD within this cohort.MethodsThe study cohort included 11,444 Uyghur adults in Xinjiang, 3rd division, from the 51st Mission. Study groups were classified according to whether GBD was present or absent at baseline. The occurrence of CVD was the end event. Demographic, anthropometric, and biochemical data were recorded, and the incidence of CVD in the GBD and non-GBD groups analysed. Cox proportional hazards regression models were used to assess the association between GBD and CVD and factors associated with their incidence. Several subgroup analyses were performed to assess CVD incidence in different subgroups. The interaction between GBD and cardiometabolic risk factors, and subsequent risk of developing CVD, was evaluated.ResultsPrevalence of GBD in the study cohort was 10.29%. After a median follow-up of 4.92 years, the cumulative incidence of CVD in the study cohort was 10.49%, 8.43% in males and 12.65% in females. CVD incidence was higher in the GBD group (34.04% vs. 7.78%, HR = 4.96, 95% CI: 4.40–5.59). After multivariate adjustment, the risk of CVD remained higher in the GBD group (HR = 2.89, 95% CI: 2.54–3.29). Subgroup analyses showed male sex, smoking, alcohol consumption, lack of exercise, and abnormal renal function were all associated with increased risk of CVD. Moreover, the risk of CVD was markedly higher in GBD combined with cardiometabolic risk factors (hypertension, T2DM, dyslipidaemia, overweight, and abdominal obesity), than in cardiometabolic risk factors alone and this was higher in the GBD group than in the non-GBD group regardless of whether cardiometabolic risk factors were combined.ConclusionGBD is an important independent risk factor for CVD development. Awareness of these associations will raise concerns among clinicians about the risk of cardiovascular disease in patients with GBD.

Trends in Cardiovascular Disease by Asian American, Native Hawaiian, and Pacific Islander Ethnicity, Medicare Health Outcomes Survey 2011-2015.

The burden of cardiovascular disease (CVD) is increasing in the aging population. However, little is known about CVD risk factors and outcomes for Asian American, Native Hawaiian, and Other Pacific Islander (NH/PI) older adults by disaggregated subgroups. Data were from the Centers for Medicare and Medicaid Services 2011-2015 Health Outcomes Survey, which started collecting expanded racial/ethnic data in 2011. Guided by Andersen and Newman's theoretical framework, multivariable logistic regression analyses were conducted to examine the prevalence and determinants of CVD risk factors (obesity, diabetes, smoking status, hypertension) and CVD conditions (coronary artery disease [CAD], congestive heart failure [CHF], myocardial infarction [MI], other heart conditions, stroke) for 10 Asian American and NH/PI subgroups and White adults. Among the 639 862 respondents, including 26 853 Asian American and 4 926 NH/PI adults, 13% reported CAD, 7% reported CHF, 10% reported MI, 22% reported other heart conditions, and 7% reported stroke. CVD risk factors varied by Asian American and NH/PI subgroup. The prevalence of overweight, obesity, diabetes, and hypertension was higher among most Asian American and NH/PI subgroups than White adults. After adjustment, Native Hawaiians had significantly greater odds of reporting stroke than White adults. More attention should focus on NH/PIs as a priority population based on the disproportionate burden of CVD risk factors compared with their White and Asian American counterparts. Future research should disaggregate racial/ethnic data to provide accurate depictions of CVD and investigate the development of CVD risk factors in Asian Americans and NH/PIs over the life course.

Increased Proportion of Sickle Cell Disease Patients Develop Cardiovascular Disease Risk Factors Following Successful Hematopoietic Cell Transplantation

Background: Hematopoietic cell transplantation (HCT) is currently the only proven curative treatment for sickle cell disease (SCD), with >90% event-free survival using a matched related donor (MRD). Long-term follow up in patients transplanted for malignant disease demonstrates a 4-fold increase in risk of developing cardiovascular disease (CVD). Risk factors for CVD include obesity, hypertension, diabetes, and dyslipidemia, which are reported in a higher incidence in both survivors of HCT and childhood malignancy. While patients with SCD typically have lower weight and blood pressure (BP) for age, cure of SCD may lead to decreased metabolic demand as well as increased weight and BP, thus uniquely predisposing post-transplant SCD subjects to CVD risk. Further, because of premature mortality due to SCD, true risk of CVD in these patients may be unknown.Objective: To investigate the development of CVD risk factors in SCD subjects who underwent HCT with myeloablative conditioning.Methods: We performed a retrospective data collection on SCD subjects who underwent allogeneic HCT at Children's Healthcare of Atlanta (CHOA) and survived to ³1 year post-HCT. Data on baseline patient and transplant characteristics as well as CVD risk factors (body mass index [BMI], BP, and cholesterol) were collected. BMI was categorized per CDC definition as underweight (<5th%), healthy weight (5th% to <85th%), overweight (85th% to <95th%), or obese (≥95th%). BP was categorized as >50th% and >90th% for patients with SCD, as per Table 1 in Pegelow et al. Pre- and post-HCT values were compared using Wilcoxon signed-rank tests or McNemar's tests, with p-values <0.05 considered statistically significant.Results: Sixty-seven SCD subjects underwent allogeneic HSCT from December 1993 to March 2016 at CHOA, 63 of whom survived to ≥1 year post-transplant. Fourteen patients did not have pre- or post-HCT BMI data available, thus were excluded from the analyses. Majority had clinically severe SCD (77.8%) and received bone marrow (93.3%) from a matched sibling donor (91.1%). Conditioning was myeloablative in all, majority using a combination of busulfan, cyclophosphamide, and anti-thymocyte globulin ± fludarabine. Patients underwent HCT at a median age of 8.8 years (range 1.8-20.3), at which time 40 (88.9%) were healthy weight, while 3 of each (6.7%) were underweight, overweight, and obese (Table 1). At last follow up (median age 10.3 years; range, 3.8-21.8), 27 patients (60.0%) were healthy weight, while 6 (13.3%) were underweight, 5 (11.1%) overweight, and 7 (15.6%) obese. When pre- and post-transplant BMI categories were compared, 66.7% of patients had no change, whereas 17.8% increased and 15.6% decreased. Of the 8 patients whose BMI category increased, 6.7% became overweight and 11.1% obese. Of the 7 patients who BMI category decreased, 2 obese patients (28.6%) became overweight, 2 overweight patients (28.6%) became obese, and 3 normal weight patients (42.9%) became underweight. BMI significantly increased from a median of 16.2 kg/m2 pre- to 19.0 kg/m2 post-HCT (p<0.001). There was no increase in the proportion of patients exceeding either the 50th or 90th percentile for systolic BP post-HCT (Figure 1). The proportion with diastolic BP exceeding 50th or 90th percentile for age for SCD was increased post-HCT compared to baseline. Five patients were diagnosed with hypertension ≥6 months post-transplant, 4 of whom were receiving treatment for chronic graft-versus-host disease (GVHD; steroids, cyclosporine [CSA], or steroids plus CSA) and 1 of whom was overweight. Routine cholesterol testing was rare, consistent with a pediatric cohort, with only 2 patients having hypercholesterolemia, both of whom were receiving treatment for chronic GVHD. Two patients had mildly elevated hemoglobin A1c levels post-HCT and none were diagnosed with diabetes. Ten patients developed chronic GVHD (22.0%), 8 of whom remained in a stable BMI category, with 1 of each either increasing or decreasing.Discussion: Following successful HCT, patients with SCD developed relative diastolic hypertension and increased BMI, both of which are known risk factors for CVD. Patients who developed chronic GVHD were more likely to be diagnosed with hypertension and/or hypercholesterolemia, although BMI category was not impacted. These data provide the rationale for longer term follow up for CVD risk factors and CVD in patients with SCD following HCT. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Subclinical Thyroid Dysfunction and the Risk of Cardiovascular Disease.

The prevalence of subclinical hypothyroidism (SH) is 3-10%. The prevalence of subclinical hyperthyroidism (SHr) is 0.7-9.7%. Thyroid hormones affect cardiac electrophysiology, contractility, and vasculature. SH is associated with an increased risk of coronary heart disease (CHD), especially in subjects under 65. SHr seems to be associated with a slightly increased risk of CHD and an increase in CHD-related mortality. Both SH and SHr carry an increased risk of developing heart failure (HF), especially in those under 65. Both SH and SHr are associated with worse prognoses in patients with existing HF. SH is probably not associated with atrial fibrillation (AF). SHr, low normal thyroid-stimulating hormone (TSH) and high normal free thyroxine (FT4) are all associated with the increased risk of AF. An association between endothelial dysfunction and SH seems to exist. Data regarding the influence of SHr on the peripheral vascular system are conflicting. SH is a risk factor for stroke in subjects under 65. SHr does not increase the risk of stroke. Both SH and SHr have an unfavourable effect on cardiovascular disease (CVD) and all-cause mortality. There is a U-shaped curve of mortality in relation to TSH concentrations. A major factor that modifies the relation between subclinical thyroid disease (SCTD) and mortality is age. SH increases blood pressure (BP). SHr has no significant effect on BP. Lipids are increased in patients with SH. In SHr, high-density lipoprotein cholesterol and lipoprotein( a) are increased. SCTD should be treated when TSH is over 10 mU/l or under 0.1 mU/l. Treatment indications are less clear when TSH is between normal limits and 0.1 or 10 mU/L. The current state of knowledge supports the understanding of SCTD's role as a risk factor for CVD development. Age is a significant confounding factor, probably due to age-associated changes in the TSH reference levels.

Impact of dyslipidemia on estimated glomerular filtration rate in apparently healthy children and adolescents: the CASPIAN-V study.

Chronic kidney disease (CKD) is a leading risk factor for development of cardiovascular disease (CVD). Dyslipidemia is also known as risk factor for CVD development. However, the association of dyslipidemia with glomerular injury among healthy children and adolescents remains controversial. We aimed to investigate the relationship between estimated glomerular filtration rate (eGFR) and lipid profile risk factors among healthy children and adolescents. In this nationwide survey, 3808 participants (1992 males, 1816 females), aged 7-18years, were selected by cluster random sampling method from 30 provinces in Iran. Body mass index (BMI) and systolic and diastolic blood pressures were measured. Blood samples were obtained for serum creatinine, fasting blood glucose, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) determinations. GFR was estimated using Schwartz equation. Girls had higher eGFR than boys (P = 0.04). In a multiple regression analysis, eGFR demonstrated a positive correlation with systolic blood pressure, BMI, fasting glucose, TC, HDL-C, and TG. By the analysis of covariance, TC, HDL-C, and TG showed a negative correlation with eGFR after adjustments for BMI, systolic and diastolic blood pressures, and fasting glucose (OR = 0.56, 95% CI =0.29-0.89). The study showed that dyslipidemia is associated with reduced eGFR among the healthy children and adolescents.

Dislipidemija u dijabetes melitusu tip 2

Type 2 diabetes mellitus is a chronic high-prevalence metabolic disease, which is characterized by hyperglycaemia, but also with lipid and protein metabolism disorders. Patients with type 2 diabetes have a high risk for cardiovascular disease (CVD) development and dyslipidemia is considered as a key marker of this increased risk. Hypertriglyceridemia, reduced high density lipoprotein cholesterol (HDL-c) concentrations, and a shift in low-density lipoprotein particles (LDL) distribution toward the small, triglycerides-rich particles, are the most important changes in the lipid profile in diabetes.Type 2 diabetes is a metabolic disorder associated with low grade inflammation and oxidative stress, so in this condition high density lipoprotein particles (HDL) also undergo structural and functional changes and, as a consequence, lose their atheroprotective role. Dyslipidemia treatment in type 2 diabetes patients younger than 40 and without any other risk factor for CVD development starts with changes in a lifestyle, but in patients older than 40 years, first line medications are statins.Glycemic and lipid control in type 2 diabetes patients significantly reduces CVD risk.

Annals for Educators - 21 August 2018.

Annals for Educators - 21 August 2018.

Hypertensive Disorders of Pregnancy and Maternal Cardiovascular Disease Risk Factor Development: An Observational Cohort Study.

Women with a history of hypertensive disorders of pregnancy (HDP) are nearly twice as likely to develop cardiovascular disease (CVD) as those who are normotensive during pregnancy. However, the emergence of CVD risk factors after HDP is less well-understood. To identify associations between HDP and maternal CVD risk factors and chart the trajectory of risk factor development after pregnancy. Observational cohort study. United States. 58671 parous NHS II (Nurses' Health Study II) participants who did not have CVD or risk factors of interest at baseline. Women were followed for self-reported physician diagnosis of chronic hypertension and hypercholesterolemia and confirmed type 2 diabetes mellitus (T2DM) from their first birth through 2013; mean follow-up ranged from 25 to 32 years across these end points. Multivariable Cox proportional hazards models estimated hazard ratios (HRs) and 95% CIs, with adjustment for prepregnancy confounders. Compared with women who were normotensive during pregnancy, those with gestational hypertension (2.9%) or preeclampsia (6.3%) in their first pregnancy had increased rates of chronic hypertension (HRs, 2.8 [95% CI, 2.6 to 3.0] and 2.2 [CI, 2.1 to 2.3], respectively), T2DM (HRs, 1.7 [CI, 1.4 to 1.9] and 1.8 [CI, 1.6 to 1.9], respectively), and hypercholesterolemia (HRs, 1.4 [CI, 1.3 to 1.5] and 1.3 [CI, 1.3 to 1.4], respectively). Although these women were more likely to develop CVD risk factors throughout follow-up, the relative risk for chronic hypertension was strongest within 5 years after their first birth. Recurrence of HDP further elevated risks for all end points. Participants self-reported HDP. Women with HDP in their first pregnancy had increased rates of chronic hypertension, T2DM, and hypercholesterolemia that persisted for several decades. These women may benefit from lifestyle intervention and early screening to reduce lifetime risk for CVD. National Institutes of Health.

Interleukin-6 as a Predictor of the Risk of Cardiovascular Disease: A Meta-Analysis of Prospective Epidemiological Studies

ABSTRACTObjective: The etiology of cardiovascular disease (CVD) is complex owing to the interactions of genetic variance with environmental factors. Inflammatory processes are now being increasingly implicated in the pathogenesis of CVD. This meta-analysis investigated the potential role of interleukin-6 (IL-6) as a risk factor for CVD development in healthy individuals.Methods: Literature search was carried out in multiple electronic databases, and study selection followed a priori eligibility criteria. Meta-analyses of standardized mean differences were carried out to determine an overall effect size of the difference in IL-6 levels between CVD cases and non-CVD matched controls. Meta-regression analyses were performed to examine the relationship between the IL-6 levels in CVD cases and several explanatory variables.Results: Seventeen studies enrolling 288738 healthy individuals with an average follow-up duration of 7.4 ± 4.1 years were found eligible. Overall, data of 5400 CVD cases and 14607 matched non-CVD controls are used in the present meta-analysis. Baseline IL-6 levels were significantly higher in CVD cases than in non-CVD controls (standardized mean difference [95% confidence interval]) of 0.14 [0.09, 0.20]/mean difference of 0.36 [0.28, 0.44] picogram per milliliter). Total cholesterol, LDL-cholesterol, and triglyceride levels were also significantly higher, and HDL-cholesterol levels were significantly lower in CVD cases in comparison with the controls. Systolic blood pressure and total cholesterol levels had a significantly positive relationship, whereas triglyceride levels had a significantly inverse relationship with the levels of IL-6.Conclusion: Higher IL-6 levels in healthy individuals are associated with CVD risk, which is co-associated with hypertension and hypercholesterolemia.

S96. CARDIOVASCULAR DISEASE RISK IN PATIENTS WITH SCHIZOPHRENIA AND BIPOLAR DISORDER

BackgroundPatients with schizophrenia and bipolar disorder have markedly reduced life expectancy compared to the general population (15–20 years). A major contributor of excess death is cardiovascular disease (CVD) [1]. During the last decade, there have been several public health campaigns for health promotion and disease prevention, and tobacco legislation has become stricter. These strategies appear to have been effective in improving the health of the general Norwegian population [2]. It is unknown whether the elevated CVD risk in patients with schizophrenia and bipolar disorder has sustained in spite of these health promotion approaches. Here we investigate the development of CVD risk factors in a large representative sample of Norwegian patients with schizophrenia and bipolar disorder between 2002 and 2017. More specifically, we explored whether the CVD risk level was similar in a cohort from 2006 and a second cohort from 2017.MethodsCross sectional analysis was performed among DSM-IV diagnosed patients included from 2002–2005 (cohort 1) and from 2006–2017 (cohort 2), respectively. Cohort 1 consisted of 161 patients with schizophrenia and 109 patients with bipolar disorder, and cohort 2 consisted of 623 patients with schizophrenia and 387 patients with bipolar disorder. Comparisons were made between cohorts regarding demographic variables, psychiatric symptoms, tobacco use, body mass index, waist circumference, total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, fasting glucose, systolic blood pressure, and diastolic blood pressure. ANCOVA was used for these analyses, with adjustments for age, duration of the disorder, and duration of psychopharmacological treatment.ResultsMean age was significantly higher for cohort 1 (35.1 years vs. 31.2 years, p < .001). There was no statistically significant difference in any of the other demographic variables or symptoms. Among patients with schizophrenia, there was no significant difference in the prevalence of CVD risk factors except from glucose being slightly increased in patients included in cohort 2 (p = .047). Among patients with bipolar disorder, there was a significant reduction in the level of total cholesterol, LDL, systolic, and diastolic blood pressure in cohort 2 (all p values < .01). These differences remained statistically significant after adjusting for age, duration of the disorder, and duration of psychopharmacological treatment.DiscussionDespite major advances in health promotion and disease prevention during the past decade, the level of CVD risk factors has remained high in patients with schizophrenia. While the level of some CVD risk factors improved in patients with bipolar disorder, they are still at increased risk of CVD. Thus, patients with severe mental disorders, especially schizophrenia, do not appear to have benefited from recent health promotion measures. Our findings also highlight the need for more effective interventions to reduce the risk of CVD in individuals with severe mental disorders, which may reduce the gap in life expectancy compared to the general population.

Association of circulating ANGPTL 3, 4, and 8 levels with medical status in a population undergoing routine medical checkups: A cross-sectional study.

PurposeAngiopoietin-like proteins (ANGPTLs) 3, 4, and 8 reportedly contribute to progression of metabolic disease, a risk factor for cardiovascular disease (CVD). The purpose of this study was to investigate whether circulating ANGPTL levels are associated with CVD risk after adjustment for potential confounding factors.MethodsWe conducted a single center, cross-sectional study of 988 Japanese subjects undergoing routine health checks. Serum ANGPTL3, 4, and 8 levels were measured using an enzyme-linked immunosorbent assay. Using multiple regression analysis we evaluated potential association of circulating ANGPTL3, 4, and 8 levels with general medical status including age, sex, smoking, drinking, obesity, hypertension, impaired glycometabolism, dyslipidemia, hyperuricemia, hepatic impairment, chronic kidney disease, anemia, cardiac abnormality, and inflammation.ResultsCirculating ANGPTL3 levels were relatively high in health-related categories of hepatic impairment and inflammation. Circulating ANGPTL4 levels were also significantly high in impaired glycometabolism or hepatic impairment but decreased in inflammation. Finally, increased ANGPTL8 levels were observed in obesity, impaired glycometabolism and dyslipidemia. Particularly, increased levels of circulating ANGPTL8 were positively correlated with circulating triglycerides and LDL-cholesterol levels and inversely correlated with circulating HDL-cholesterol levels.ConclusionsCirculating ANGPTL3, 4, and 8 levels reflect some risk factors for CVD development.

Clinical impact of sedentary behaviors in adult survivors of acute lymphoblastic leukemia: A report from the St. Jude Lifetime Cohort study.

Sedentary behaviors are associated with poor health outcomes in the general population, but their clinical impact on adult survivors of childhood acute lymphoblastic leukemia (ALL) has not been characterized to date. In the current study, we described the prevalence of sedentary behaviors in survivors of ALL and examined associations between time spent sedentary and body composition and onset of cardiovascular disease (CVD) risk factors. Participants' self-reported screen time (eg, television, computer) and activity as measured by accelerometer were used to determine activity time (sedentary, light activity, and moderate or vigorous physical activity). The percentage of time spent in each activity was compared between 331 survivors of ALL and 330 controls. Associations between time sedentary and body composition were evaluated in survivors using linear regression models. Cox proportional hazard models were used to examine the association between time sedentary at baseline and CVD risk factor onset during follow-up. Survivors spent approximately 65% of their time sedentary, 32% in light activity, and 2% in moderate or vigorous physical activity compared with 67% (P = .04), 30% (P<.01), and 3% (P<.01), respectively, in controls. Among survivors, percentage lean body mass decreased by 1.0% ± 0.4% (P = .01) per 10% increase in time sedentary. Survivors who were sedentary ≥60% per day were found to be at an increased risk of high total cholesterol (hazard ratio, 2.52; 95% confidence interval, 1.12-5.64) and any CVD risk factor (hazard ratio, 1.96; 95% confidence interval, 1.16-3.30). Sedentary behavior is associated with low lean mass and CVD risk factor development and should be limited in survivors of childhood ALL. Cancer 2018;124:1036-43. © 2017 American Cancer Society.

Neighbourhood disadvantage and behavioural problems during childhood and the risk of cardiovascular disease risk factors and events from a prospective cohort.

Both low socioeconomic status (SES) and behavioural problems in childhood are associated with cardiovascular disease (CVD) in adulthood, but their combined effects on CVD are unknown. Study objectives were to investigate the effect of neighbourhood level SES and behavioural problems during childhood on the development of CVD risk factors and events during adulthood. Participants were from a longitudinal cohort (n = 3792, baseline: 6–13 years of age) of Montreal children, followed from 1976 to 2010. SES was a composite measure of neighbourhood income, employment, education, and single-parent households separately assessed from census micro data sets in 1976, 2001, and 2006. Behavioural problems were assessed based on sex-specific peer assessments. CVD events were from medical records. Sex-stratified multivariable Cox regression models adjusted for age, frequency of medical visits, and parental history of CVD. Males from disadvantaged neighbourhoods during childhood were 2.06 (95% CI: 1.09–3.90, p = 0.03) and 2.51 (95% CI: 1.49–4.22, p = 0.0005) times more likely to develop a CVD risk factor or an event, respectively, than males not from disadvantaged neighbourhoods. Aggressive males were also 50% more likely to develop a CVD risk factor or event. Females from disadvantaged neighbourhoods during childhood were 1.85 (95% CI: 1.33–2.59, p = 0.0003) times more likely to develop a CVD risk factor. Future studies should aim to disentangle the interpersonal from the socioeconomic effects on CVD incidence.

Preterm Delivery and Maternal Cardiovascular Disease in Young and Middle-Aged Adult Women.

Preterm delivery has been shown to be associated with increased risk of cardiovascular disease (CVD), but it is unknown whether this risk remains after adjustment for prepregnancy lifestyle and CVD risk factors. We examined the association between history of having delivered an infant preterm (<37 weeks) and CVD in 70 182 parous women in the Nurses' Health Study II. Multivariable Cox proportional-hazards models were used to estimate hazards ratios (HRs) and 95% confidence intervals (CIs) for CVD events (myocardial infarction and stroke, n=949); we also adjusted for intermediates to determine the proportion of the association between preterm and CVD accounted for by postpartum development of CVD risk factors. After adjusting for age, race, parental education, and prepregnancy lifestyle and CVD risk factors, preterm delivery in the first pregnancy was associated with an increased risk of CVD (HR, 1.42; 95% CI, 1.16-1.72) in comparison with women with a term delivery (≥37 weeks) in the first pregnancy. When preterm delivery was split into moderate preterm (≥32 to <37 weeks) and very preterm (<32 weeks), the HRs were 1.22 (95% CI, 0.96-1.54) and 2.01 (95% CI, 1.47-2.75), respectively. The increased rate of CVD in the very preterm group persisted even among women whose first pregnancy was not complicated by hypertensive disorders of pregnancy (HR, 2.01; 95% CI, 1.38-2.93). In comparison with women with at least 2 pregnancies, all of which were delivered at term, women with a preterm first birth and at least 1 later preterm birth had a HR of CVD of 1.65 (95% CI, 1.20-2.28). The association between moderate preterm first birth and CVD was accounted for in part by the development of postpartum chronic hypertension, hypercholesterolemia, type 2 diabetes mellitus, and changes in body mass index (proportion accounted for, 14.5%; 95% CI, 4.0-41.1), as was the very-preterm-CVD relationship (13.1%; 95% CI, 9.0-18.7). Preterm delivery is independently predictive of CVD and may be useful for CVD prevention efforts. Because only a modest proportion of the preterm-CVD association was accounted for by development of conventional CVD risk factors, further research may identify additional pathways.

Dyslipidemia in patients with chronic kidney disease: etiology and management.

Patients with chronic kidney disease (CKD), including those with end-stage renal disease, treated with dialysis, or renal transplant recipients have an increased risk for cardiovascular disease (CVD) morbidity and mortality. Dyslipidemia, often present in this patient population, is an important risk factor for CVD development. Specific quantitative and qualitative changes are seen at different stages of renal impairment and are associated with the degree of glomerular filtration rate declining. Patients with non-dialysis-dependent CKD have low high-density lipoproteins (HDL), normal or low total cholesterol (TC) and low-density lipoprotein (LDL) cholesterol, increased triglycerides as well as increased apolipoprotein B (apoB), lipoprotein(a) (Lp (a)), intermediate- and very-low-density lipoprotein (IDL, VLDL; “remnant particles”), and small dense LDL particles. In patients with nephrotic syndrome lipid profile is more atherogenic with increased TC, LDL, and triglycerides. Lipid profile in hemodialysis (HD) patients is usually similar to that in non-dialysis-dependent CKD patients. Patients on peritoneal dialysis (PD) have more altered dyslipidemia compared to HD patients, which is more atherogenic in nature. These differences may be attributed to PD per se but may also be associated with the selection of dialytic modality. In renal transplant recipients, TC, LDL, VLDL, and triglycerides are elevated, whereas HDL is significantly reduced. Many factors can influence post-transplant dyslipidemia including immunosuppressive agents. This patient population is obviously at high risk; hence, prompt diagnosis and management are required to improve their clinical outcomes. Various studies have shown statins to be effective in the cardiovascular risk reduction in patients with mild-to-moderate CKD as well as in renal transplant recipients. However, according to recent clinical randomized controlled trials (4D, A Study to Evaluate the Use of Rosuvastatin in Subjects on Regular Dialysis: an Assessment of Survival and Cardiovascular Events, and Study of Heart and Renal protection), these beneficial effects are uncertain in dialyzed patients. Therefore, further research for the most suitable treatment options is needed.