Framingham 10-year Cardiovascular Risk Score Research Articles

#1479 Single nucleus RNA-sequencing indicates functional heterogeneity of renal endothelial cells in chronic kidney disease

Abstract Background and Aims The burden of cardiovascular disease (CVD) in patients with chronic kidney disease (CKD) remains very high. Endothelial cell (EC) dysfunction is an important key player in the initiation and progression of both pathologies. More importantly, endothelial dysfunction occurs early in both disease courses and is potentially reversible, making it a promising target for effective preventive strategies. Recently, accumulating single-cell RNA sequencing-based evidence has highlighted EC heterogeneity in different pathophysiological contexts. However, while biological processes such as systemic inflammation, oxidative stress fibrosis are being defined as comm EC in CKD and CVD, a comprehensive understanding of at single-cell resolution is lacking. Here, we characterized renal EC subpopulations by single-nucleus RNA sequencing (snRNA-seq) to investigate alterations in CKD patients healthy controls and identify potential drivers of EC dysfunction in CKD. Method Droplet-based snRNA-seq (10X Genomics Chromium) was performed on cryopreserved kidney biopsy cores from 6 human patients with CKD (eGFR < 45 mL/min/1.73 m2) and 3 healthy controls. CKD patients included 2 patients with primary focal segmental glomerulosclerosis (FSGS) and 4 with secondary/maladaptive FSGS (2 patients with diabetes mellitus, 2 female patients in total); all patients had a Framingham 10-year cardiovascular risk score > 20, but no established CVD. Healthy control samples were pre-perfusion biopsies from patients undergoing living kidney donation (including 2 female patients). EC subclusters were annotated based on the expression of canonical EC marker genes. Differential gene expression analysis for patient samples vs. controls included all ECs and DEGs were filtered for log2FC > 0.25 or < −0.25 and adjusted P-value of < .05. Gene set enrichment analysis (GSEA) on the identified DEGs was performed using GO terms. Results A total of 4 081 ECs were present in the dataset, consisting of 5 EC subtypes in both the patient and control cohorts (Panel A). DEGs in CKD patients vs. controls included upregulated genes related to organogenesis and cell differentiation (MEF2C, MEIS2), vascular development (FLRT2), and angiogenesis regulators (VEGFC, PRCP, HDAC9) (Panel B). Notably, VEGFC and FLRT2, are involved in directing EC motility and vascular patterning. In accordance, GSEA showed enrichment for GO biological processes related to vascular endothelial growth factor signaling pathway, endothelial cell differentiation, endothelial development, regulation of angiogenesis, and endothelial cell migration (Panel C). This suggests a potential link between these genes and aberrant angiogenesis, analogous to previous findings in diabetic nephropathy. Some but not all of these changes were also reported for renal ECs of early diabetic nephropathy patients. Of note, the majority of patients studied in our cohort were non-diabetic, warranting further investigation into renal endothelial cell transcriptional alterations that are general to renal disease or specific to particular renal conditions such as diabetic nephropathy. Differential gene expression and GSEA analysis of the EC subclusters in CKD indicated involvement of the peritubular capillary and ascending vasa recta ECs in EC migration / angiogenesis-related responses, overlapping with the overall analysis described above. Glomerular capillary ECs showed upregulation of immune-related genes and processes, reflecting the inflammatory status of the kidney disease. Conclusion snRNA-seq analysis revealed heterogeneity and subtype-specific gene expression alterations of renal ECs from CKD patients compared to healthy controls. Differential functions include enhanced angiogenic (potentially compensatory) and immune-related responses. These findings suggest that specific biological functions may direct different roles of the renal EC subtypes in CKD and will be further validated for their cluster-specificity and for their therapeutic relevance.

Prevalence of lifestyle cardiovascular risk factors and estimated framingham 10-year risk scores of adults with psychotic disorders compared to controls at a referral hospital in Eldoret, Kenya

IntroductionLifestyle factors such as smoking, alcohol use, suboptimal diet, and inadequate physical activity have been associated with increased risk of cardiovascular diseases. There are limited data on these risk factors among patients with psychosis in low- and middle-income countries.ObjectivesThis study aimed to establish the prevalence of lifestyle cardiovascular risk factors, and the 10-year cardiovascular risk scores and associated factors in patients with psychosis compared to controls at Moi Teaching and Referral Hospital in Eldoret, Kenya.MethodsA sample of 297 patients with schizophrenia, schizoaffective disorder, or bipolar mood disorder; and 300 controls matched for age and sex were included in this analysis. A study specific researcher-administered questionnaire was used to collect data on demographics, antipsychotic medication use, smoking, alcohol intake, diet, and physical activity. Weight, height, abdominal circumference, and blood pressure were also collected to calculate the Framingham 10-year Cardiovascular Risk Score (FRS), while blood was drawn for measurement of glucose level and lipid profile. Pearson’s chi-squared tests and t-tests were employed to assess differences in cardiovascular risk profiles between patients and controls, and a linear regression model was used to determine predictors of 10-year cardiovascular risk in patients.ResultsCompared to controls, patients with psychosis were more likely to have smoked in their lifetimes (9.9% vs. 3.3%, p = 0.006) or to be current smokers (13.8% vs. 7%, p = 0.001). Over 97% of patients with psychosis consumed fewer than five servings of fruits and vegetables per week; 78% engaged in fewer than three days of vigorous exercise per week; and 48% sat for more than three hours daily. The estimated 10-year risk of CVD was relatively low in this study: the FRS in patients was 3.16, compared to 2.93 in controls. The estimated 10-year cardiovascular risk in patients was significantly associated with female sex (p = 0.007), older patients (p < 0.001), current tobacco smoking (p < 0.001), and metabolic syndrome (p < 0.001).ConclusionIn the setting of Eldoret, there is suboptimal physical exercise and intake of healthy diet among patients with psychosis and controls. While the estimated risk score among patients is relatively low in our study, these data may be useful for informing future studies geared towards informing interventions to promote healthy lifestyles in this population.

Effects of Framingham 10-Year Cardiovascular Risk Score and Viral Load on Brain Integrity in Persons With HIV.

Combination antiretroviral therapy (cART) has allowed for viral load (VL) suppression and increased life expectancy for persons with HIV (PWH). Altered brain integrity, measured by neuropsychological (NP) performance and neuroimaging, is still prevalent among virally suppressed PWH. Age-related conditions such as cardiovascular disease may also affect brain integrity. This study investigated the effects of cardiovascular risk, VL, and HIV serostatus on cerebral blood flow (CBF), brain volumetrics, and cognitive function in PWH and persons without HIV (PWoH). Ten-year cardiovascular risk, using the Framingham Heart Study criteria, was calculated in PWH (n = 164) on cART with undetectable (≤20 copies/mL; n = 134) or detectable (>20 copies/mL; n = 30) VL and PWoH (n = 66). The effects of cardiovascular risk on brain integrity (CBF, volume, and cognition) were compared for PWH (undetectable and detectable VL) and PWoH. PWH had smaller brain volumes and worse NP scores than PWoH. PWH with detectable and undetectable VL had similar brain integrity measures. Higher cardiovascular risk was associated with smaller volumes and lower CBF in multiple brain regions for PWH and PWoH. Significant interactions between HIV serostatus and cardiovascular risk on brain volumes were observed in frontal, orbitofrontal, and motor regions. Cardiovascular risk was not associated with cognition for PWH or PWoH. Neuroimaging, but not cognitive measures, was associated with elevated cardiovascular risk. HIV serostatus was associated with diminished brain volumes and worse cognition while CBF remained unchanged, reflecting potential protective effects of cART. Neuroimaging measures of structure (volume) and function (CBF) may identify contributions of comorbidities, but future longitudinal studies are needed.

Periventricular white matter hyperintensity burden and cognitive impairment in early Parkinson's disease.

This study quantified the total brain and periventricular white matter hyperintensity (WMH) burdens in patients with early Parkinson's disease (PD) and explored their associations with cardiovascular risk factors and cognitive performance. A total of 175 non-demented patients with early PD who had undergone baseline brain magnetic resonance imaging were included. Comprehensive neurocognitive testing was conducted to identify PD with mild cognitive impairment (PD-MCI) and to evaluate performances in individual cognitive domains. Cardiovascular risk was expressed as a modified Framingham 10-year cardiovascular risk score (mFRS). A total of 53.7% of this early PD cohort fulfilled the diagnostic criteria for PD-MCI. An increase in mFRS was significantly associated with increases in the total brain WMH (P=0.015) and periventricular WMH (P=0.040) burden, independent of age and gender. The periventricular WMH burden was significantly associated with PD-MCI (P=0.046) in early PD, independent of cardiovascular risk factors. Patients in the 5th quintile of periventricular WMH burden were 8.6 times more likely to have PD-MCI compared with patients in the 1st quintile of periventricular WMH burden (P=0.004). However, total brain WMH burden was not associated with PD-MCI (P=0.158). In individual cognitive domains, heavier periventricular WMH burden was associated with worse executive function and visuospatial function independent of cardiovascular risk factors. Periventricular WMHs are a useful imaging biomarker for cognitive impairment in early PD. Cardiovascular risk factors, although associated with periventricular WMHs, were unable to fully explain the association between periventricular WMHs and cognitive impairment in early PD.

LONELINESS, AGE, CARDIOVASCULAR AND METABOLIC HEALTH IN SCHIZOPHRENIA

Introduction Loneliness is common in schizophrenia with prevalence estimates as high as 80% among people with schizophrenia. Recent studies among non-psychiatric samples have indicated deleterious effects of loneliness on physical health and mortality, including increased risk of hypertension, central obesity, metabolic syndrome, coronary heart disease, stroke, and other cardiovascular disorders. The all-cause mortality risk of loneliness is double that from obesity and equivalent to that from smoking ¾ of a pack of cigarettes per day. However, despite the increased risk for loneliness and cardiovascular problems in schizophrenia, these associations have not been examined directly in previous studies of people with schizophrenia. This study aims to explore the relationship of loneliness and age with cardiovascular and metabolic markers of physical health among participants with schizophrenia in comparison to non-psychiatric comparison (NC) participants. Methods The third edition of the University of California, Los Angeles Loneliness Scale (UCLA-3) was administered to 53 participants with schizophrenia, as diagnosed by DSM IV criteria, and 32 NC participants. Sociodemographic and clinical characteristics such as age, education, gender, duration of illness, and antipsychotic use were measured. Participants were also evaluated in terms of severity of psychopathology (positive, negative, depressive, and anxiety symptoms) using standard clinical symptom rating scales. Metabolic and cardiovascular health markers including LDL, HDL, total cholesterol, triglycerides, homeostatic model assessment of insulin resistance (HOMA-IR), systolic and diastolic blood pressure, fasting glucose, as well as waist circumference, body mass index were also collected. The Framingham 10-year Cardiovascular risk score was also calculated. This data was drawn from a larger ongoing study of aging in schizophrenia. We included only those participants with complete data for all of the above measures in the present analyses. Differences between the two groups on continuous variables were evaluated with independent t-tests; differences on categorical variables were evaluated with Pearson's Chi-square. Within each group, we also employed hierarchical multiple regression analyses to evaluate the association of loneliness with each health marker, while adjusting for gender and age. We also examined interactions between age and loneliness. (Given that loneliness is associated with an increased risk of mortality, the presence or absence of the latter could indicate potential survivor biases in the sample.) Results Participants with schizophrenia had a mean age of 51.41 (SD 11.03), with 20(37.7%) females, and 28 (52.8%) non-Caucasians. The NC participants had a mean age of 51.52 (SD 9.98), with 19 (59.4%) females, and 20 (62.5%) non- Caucasians. Relative to the NC group, participants with schizophrenia had worse loneliness, as well as worse positive, negative, depressive and anxiety symptoms. The also had fewer years of education, higher 10- year risk of cardiovascular disease, and were more likely to meet criteria for metabolic syndrome. Among the NC group, multivariate analyses indicated no association of loneliness with of any of the physical health measures, although the association of loneliness with total cholesterol suggested a non-trivial amount of shared variance (R2= 0.85, p= .086). Within the schizophrenia group, loneliness was associated with worse triglyceride levels; there was no age*loneliness interactions for most variables, suggesting the association was similar across age levels. However, there were significant loneliness x age interactions for cholesterol, t = -2.40, p = .021, R2 = .102, and LDL levels, t = -2.67, p = .011, R2 = .129. Specifically, loneliness was associated with worse cholesterol levels among individuals 1 SD below the mean in age (i.e., age 40.39), t= 2.30, p= .020, and better LDL levels among individuals 1 SD above the mean age (i.e., age 62.45), t= -2.037, p= .047. Conclusions Given the small sample size (particularly among NCs), and the exploratory nature of the present analyses, findings must be interpreted with caution until replicated in larger independent samples. However, the overall pattern of findings within the schizophrenia group is intriguing in suggesting a possible link between loneliness and blood lipid levels. There have been some GWAS studies suggesting an overlap in polygenic risk scores for cholesterol and loneliness. The differential effects of loneliness on cholesterol measures among older versus younger patients must be interpreted with particular caution, but if replicated could indicate those people with schizophrenia who survive to older age have a protective factor moderating the association of loneliness and cholesterol levels. The latter warrants further prospective research among older and younger people with schizophrenia. This research was funded by: Support provided by National Institute of Mental Health (NIMH) grant 5R01 MH094151-04 (Jeste), the NIMH T32 Geriatric Mental Health Program MH019934 (PI: Jeste), and UC San Diego's Stein Institute for Research on Aging (Director: Jeste).

Fatty liver in Pakistani cohort with rheumatoid arthritis.

Objective:To determine the frequency of fatty liver (non-alcoholic) disease, Framingham 10-year cardiovascular risk score in rheumatoid arthritis patients.Methods:This study was conducted from September 1st to March 19, 2019, at Rheumatology OPD, Central Park Medical College Lahore. One hundred ninety two seropositive rheumatoid arthritis patients were recruited. Demographic details were noted, BP, BMI, smoking habits, and waist circumference were noted, then sent to radiology department for ultrasound scan of abdomen by an expert radiologist. On next day 10 ml blood was taken by phlebotomist for lipid profile and fasting blood sugar levels, after availability of results 10-years Framingham cardiovascular risk score was calculated.Results:Females were (81.3%) mean age of (45.4) years, fatty liver was present in n=39 (20.3%). In positive cases comorbid like metabolic syndrome was present (71.8%), diabetes mellitus (33.3%), hypertension (59%) FRS score (intermediate to high in (33.3%), history of hakeem/desi medication use (51.3%), while on regression analysis all study parameters except DMARD’s had significant association with fatty liver (p<0.05).Conclusion:Nonalcoholic fatty liver disease is very widely prevalent in rheumatoid arthritis patients. As in general population, it is multifactorial in origin and needs careful monitoring and treatment.

Effects of a Stress Management Program Based on Psychological Risk Factors of Cardiovascular Disease after Retirement in an Underpopulated Area: A Pilot Study

Background: To develop an effective health education program to prevent cardiovascular disease in middle-aged residents after retirement in underpopulated areas, we explored the effects of a stress management program based on the type A behavior pattern. Methods: This study was carried out in a rural city in Japan recognized as underpopulated and participants were civil servants aged 45 - 64 who joined a stress management program offered as part of staff training. Learning materials for the program were developed based on the type A behavior pattern. Measures for the impact evaluation were Bloom’s learning domains and stage of change for stress management practice. Measures for the outcome evaluation were KG’s Daily Life Questionnaire (KG Questionnaire), the Hospital Anxiety and Depression Scale (HADS) and the Framingham 10-year cardiovascular risk score (CVD risk score). We statistically analyzed changes in each item between time points. Results: Eighteen participants completed questionnaire surveys at pre-, post-, and 4 weeks post-program and eleven had complete blood pressure and weight measurements at pre- and post-program. In the impact evaluation, the Friedman test found significant differences between the three time points in all of Bloom’s learning domain scores and stage of change for stress management. In the post hoc analysis, a significant increase was seen between pre- and post-program and between pre- and 4 weeks post-program in cognitive domain score, psychomotor domain score and stage of change for stress management. In the outcome evaluation, a significant decrease in systolic blood pressure was seen between pre- and post-program. Conclusion: The present study suggested that a stress management program using learning materials based on type A behavior could promote stress management practices and reduce the risk of cardiovascular disease. This stress management program is expected to be useful as a health promotion activity for middle-aged residents after retirement in underpopulated areas.

Diabetes screening intervals based on risk stratification.

BackgroundGuidelines for frequency of Type 2 diabetes mellitus (DM) screening remain unclear, with proposed screening intervals typically based on expert opinion. This study aims to demonstrate that HbA1c screening intervals may differ substantially when considering individual risk for diabetes.MethodsThis was a multi-institutional retrospective open cohort study. Data were collected between April 1999 to March 2014 from one urban and one rural cohort in Japan. After categorization by age, we stratified individuals based on cardiovascular disease risk (Framingham 10-year cardiovascular risk score) and body mass index (BMI). We adapted a signal-to-noise method for distinguishing true HbA1c change from measurement error by constructing a linear random effect model to calculate signal and noise of HbA1c. Screening interval for HbA1c was defined as informative when the signal-to-noise ratio exceeded 1.ResultsAmong 96,456 healthy adults, 46,284 (48.0%) were male; age (range) and mean HbA1c (SD) were 48 (30–74) years old and 5.4 (0.4)%, respectively. As risk increased among those 30–44 years old, HbA1c screening intervals for detecting Type 2 DM consistently decreased: from 10.5 (BMI <18.5) to 2.4 (BMI > 30) years, and from 8.0 (Framingham Risk Score <10%) to 2.0 (Framingham Risk Score ≥20%) years. This trend was consistent in other age and risk groups as well; among obese 30–44 year olds, we found substantially shorter intervals compared to other groups.ConclusionHbA1c screening intervals for identification of DM vary substantially by risk factors. Risk stratification should be applied when deciding an optimal HbA1c screening interval in the general population to minimize overdiagnosis and overtreatment.

Overview of saxagliptin efficacy and safety in patients with type 2 diabetes and cardiovascular disease or risk factors for cardiovascular disease.

Most individuals with type 2 diabetes mellitus have or will develop multiple independent risk factors for cardiovascular disease, particularly coronary artery disease (CAD). CAD is the leading cause of morbidity and mortality among individuals with type 2 diabetes mellitus, and treating these patients is challenging. The risk of hypoglycemia, weight gain, or fluid retention with some diabetes medications should be considered when developing a treatment plan for individuals with a history of CAD or at risk for CAD. Dipeptidyl peptidase-4 inhibitors are oral antihyperglycemic agents that inhibit the breakdown of the incretin hormones glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide, resulting in increased glucose-dependent insulin secretion and suppression of glucagon secretion. Saxagliptin is a potent and selective dipeptidyl peptidase-4 inhibitor that improves glycemic control and is generally well tolerated when used as monotherapy and as add-on therapy to other antihyperglycemic medications. This review summarizes findings from recently published post hoc analyses of saxagliptin clinical trials that have been conducted in patients with and without a history of cardiovascular disease and in patients with and without various risk factors for cardiovascular disease. The results show that saxagliptin was generally well tolerated and consistently improved glycemic control, as assessed by reductions from baseline in glycated hemoglobin, fasting plasma glucose concentration, and postprandial glucose concentration, regardless of the presence or absence of baseline cardiovascular disease, hypertension, statin use, number of cardiovascular risk factors, or high Framingham 10-year cardiovascular risk score.