Lower Prevalence Of Cardiovascular Disease Research Articles

#1804 Long-term outcomes of CKD patients with lupus nephritis: a nationwide cohort study

Abstract Background and Aims Health trajectories of patients with lupus nephritis (LN) are poorly understood in the setting of moderate and advanced chronic kidney disease (CKD). Furthermore, data on comparison of outcomes of LN to other forms of CKD are scarce. Therefore, the aim of this study was to compare long-term outcomes between LN and CKD from other etiologies. Method Using data from the Swedish Renal Registry (2006-2021), we compared clinical outcomes between patients with moderate and advanced CKD related to LN (LN-CKD), and patients with CKD due to primary glomerular diseases (PGD-CKD, i.e. IgA nephropathy, focal segmental glomerulosclerosis, membranous nephropathy), and due to other common CKD etiologies with high cardiovascular risk (Other-CKD, mostly diabetes and nephrosclerosis). Cox proportional hazard models were used to estimate the adjusted hazard ratios of mortality, major cardiovascular events (MACE), heart failure (HF), kidney replacement therapy (KRT) and acute kidney injury (AKI). Models were adjusted for age, sex, comorbidities, clinical and biological data including kidney function, medications and healthcare utilization. Results At baseline, patients with LN-CKD (N = 317, 61 years, 76% women, median eGFR 30 mL/min per 1.73 m²) and PGD-CKD (N = 2296, 57 years, 30% women, eGFR 29 mL/min per 1.73 m²), were younger and had lower prevalence of cardiovascular disease than patients with Other-CKD (N = 34778, 75 years, 36% women, eGFR 25 mL/min per 1.73 m²). Over a median follow-up of 6.2 [3.3; 9.8] years, 19029 deaths (51%), 15768 (42%) MACE and 8390 (22%) KRT events occurred. The unadjusted 5-year absolute risks of death and MACE were high both in patients with LN-CKD (27% and 25%) and Other-CKD (50% and 44%), but lower in those with PGD-CKD (16% and 14%), whereas the 5-year absolute KRT risk was higher in patients with PGD-CKD (PGD-CKD: 37%, LN-CKD: 23%, Other-CKD: 23%). In multivariable analyses and as compared to PGD-CKD, patients with LN-CKD had a higher risk of death (adjusted HR: 1.63 [95% CI: 1.32-2.02]), MACE (1.65 [1.31-2.08]), HF (1.68 [1.31-2.14]) and AKI (1.45 [1.02-2.05]) and showed a lower risk of KRT (HR: 0.81 [0.64-1.02]), although the 95% CI slightly overlapped (Figure, panel A). In contrast, the risks of adverse events were similar between patients with LN-CKD and those with Other-CKD (Figure, panel B). Conclusion While LN-CKD had a lower risk of KRT than PGD-CKD, they exhibited a higher risk of death, MACE, KRT, HF and AKI, reaching the risk magnitude of patients with high cardiovascular burden (Other-CKD). Our findings may inform decisions for care planning in patients with advanced CKD and LN.

Phenotypes Associated with HFE p.C282Y Homozygosity, the Main Hereditary Hemochromatosis Genotype, in Four Large Genetic Cohorts

Introduction Hereditary hemochromatosis (HH) is the most common known recessive hereditary disease in people of northern European descent. HH is most commonly caused by the HFE-C282Y homozygosity. Disease penetrance is highly variable (1-20%). We have examined the association between C282Y homozygosity and multiple phenotypes, both case-control and quantitative, across 4 international cohorts (deCODE genetics, UK Biobank, Denmark (Copenhagen Hospital Biobank / Danish Blood Donor Study) and Intermountain Healthcare) in an effort to shed a new light on the pathophysiology of this common hereditary disease. Methods We preformed a phenome wide association study meta-analyses for C282Y homozygosity across the 4 beforementioned cohorts, comprising around 970.000 individuals, of those 5928 were homozygous for the C282Y mutation (746 in deCODE/Iceland MAF 6.71%, 2865 in UK Biobank MAF 7.94%, 1703 in CHB MAF 5.6% and 614 in Intermountain Healthcare MAF 6.19%). The analyses comprised both case-control phenotypes (approximately 7000), cases being defined by ICD-10 codes, and continuous quantitative phenotypes (approximately 5500), both results from blood tests and proteome data from deCODE and UK Biobank. Results C282Y homozygotes had a higher prevalence of the following liver, hematological and rheumatic diseases compared to a control group with no copy of the C282Y variant. Diagnosed fibrosis and cirrhosis of liver (odds ratio 4.30, 95% confidence interval 3.35 to 5.51, p=1.77x10 -30), liver cell carcinoma (9.04, 6.01 to 13.58, p=3.24x10 -26) and fatty liver disease (1.75, 1.45 to 2.11, p=5.42x10 -09) were strikingly more common in C282Y homozygotes. Unsurprisingly C282Y homozygotes also had higher liver parameters. Notably C282Y homozygotes had a higher prevalence of diagnosed polycythemia vera (7.24, 4.93 to 10.62, p=4.37x10 -24) yet no association was found with clonal hematopoiesis (1.09, 0.88 to 1.34, p=4.47x10 -01). Strong association was found between C282Y homozygosity and increased hemoglobin (0.41 standard deviations, 95% confidence interval 0.38 to 0.45, p=6.84x10 -142), MCH (0.98, 0.93 to 1.03, p=<1.00x10 -300) and MCV (0.82, 0.78 to 0.86, p=<1.00x10 -300). Red blood cell count (RBC) was decreased (-0.27, -0.30 to -0.23, p=1.06x10 -50), while reticulocyte count (0.30, 0.26 to 0.34, p=1.42x10 -54) and percentage (0.36, 0.32 to 0.40, p=7.91x10 -79) were increased. Erythropoietin (EPO) measurements were markedly decreased in C282Y homozygotes (-0.31, -0.40 to -0.22, p=1.77x10 -11). Homozygous individuals had an increased risk of being diagnosed with osteoarthritis of hip (1.83, 1.63 to 2.07, p=4.30x10 -23) and were more likely to undergo total hip replacement (2.00, 1.69 to 2.29, p=5.81x10 -18). In contrast to these risk enhancing effects C282Y homozygotes had a lower prevalence of cardiovascular disease (CVD). C282Y homozygotes had decreased risk of coronary artery disease (CAD) (0.79, 0.72 to 0.86, p=4.26x10 -07) and angina pectoris (0.77, 0.69 to 0.86, p=4.28x10 -06) and were less likely to undergo coronary artery bypass graft (0.60, 0.49 to 0.74, p=2.39x10 -06). Pure hypercholesterolemia (0.76, 0.69 to 0.83, p=2.52x10 -09) and disorders of lipoprotein metabolism (0.75, 0.66 to 0.85, p=8.41x10 -06) was less commonly diagnosed. C282Y homozygotes were less likely to take cholesterol lowering statin drugs (0.74, 0.67 to 0.81, p=1.45x10 -09). Unsurprisingly with regard to these results strong association was found with lower cholesterol measurements in C282Y homozygotes, the effects being most pronounced on LDL cholesterol (-0.38, -0.42 to -0.35, p=1.61x10 -99). Total cholesterol was also markedly lowered (-0.35, -0.38 to -0.31, p=1.38x10 -91), as well as non HDL cholesterol (-0.34, -0.37 to -0.30, p=2.36x10 -81). No significant association was found with HDL cholesterol and triglyceride measurements. Conclusions C282Y homozygosity was associated with significantly increased risk of liver disease, liver cell carcinoma and osteoarthritis of hip. Homozygous individuals had increased risk of non-clonal primary polycythemia, association with polycythemia vera likely due to misdiagnosis or early diagnosis exacerbated by significantly increased hemoglobin. C282Y homozygotes had a significant decrease in LDL, non-HDL and total cholesterol measurements and were protected against cardiovascular disease.

The association between local area immigrant fraction and prevalence of cardiovascular diseases in the United States: an observational study

Local area immigrant fraction is strongly and positively correlated with local life expectancy in the United States. The aim of the study was to determine the relationship between local area immigrant fraction and local prevalence of coronary heart disease (CHD) and stroke. Cross-sectional study design, with ZIP code as the unit of observation. Demographic data was obtained from the American Community Survey, and linked to indicators of health access (e.g., insurance, annual check-ups, cholesterol screening), obesity, behavior (smoking, exercise), and cardiovascular outcomes data from the 2020 Population Level Analysis and Community Estimates. Multivariable regression and path analyses were used to assess both direct and indirect relationships among variables. CHD prevalence was lower in the second (3.9% relative difference, 95% CI: 3.1-4.5%), third (6.5%, 95% CI: 5.8-7.1%), and fourth (14.8%, 95% CI: 14.1-15.8%) quartiles of immigrant fraction compared to the lowest (p-trend <0.001). These effects remained robust in multivariable analysis following adjustment for indicators of access, obesity, and behavioral variables (p-trend <0.0001). For stroke, only the highest quartile demonstrated a significant difference in prevalence (2.1%, 95% CI: 1.2-3.0% with full adjustment). In CHD path analysis, ∼45% of the association of immigrant fraction was direct, and ∼55% was mediated through lower prevalence of deleterious behaviors (e.g., smoking). In stroke path analysis, the effect was entirely mediated through indirect effects. In the United States, ZIP codes with higher immigrant fractions have lower prevalence of cardiovascular diseases. These associations are partially mediated through differences in health behaviors at the community level. NIH (K08CA252635, P30AG0059304, K24HL150476), Stanford University, Rutgers University.

#2710 SEX DIFFERENCE IN CARDIOVASCULAR RISK IN PATIENTS WITH CHRONIC KIDNEY DISEASE: A POOLED ANALYSIS OF FOUR COHORT STUDIES

Abstract Background and Aims Progression of chronic kidney disease (CKD) has proven to be faster in men than in Women [1-3]. Whether the same holds true for cardiovascular risk remains ill-defined. Method We conducted a pooled analysis of 4 cohort studies from 40 nephrology clinics in Italy including patients with CKD (estimated GFR&amp;lt;60 ml/min/1.73m2 or higher if proteinuria &amp;gt;0.15 g/day). The aim was to compare multivariable-adjusted risk (Hazard Ratio, 95% Confidence Interval) of a composite cardiovascular endpoint (cardiovascular death and non-fatal myocardial infarction, congestive heart failure, stroke, revascularization, peripheral vascular disease, and nontraumatic amputation) in women (n = 1,192) versus men (n = 1,635). Results At baseline, women had slightly higher systolic blood pressure (SBP) as compared with men (139±19 vs 138±18 mmHg, P = 0.049), lower eGFR (33.4 vs 35.7 mL/min/1.73 m2 , P = 0.001) and lower urine protein excretion (0.30 g/day vs 0.45 g/day in men, P&amp;lt;0.001). Women did not differ from men in age and prevalence of diabetes while having a lower prevalence of cardiovascular disease, left ventricular hypertrophy and smoking habit. During a median follow-up of 4.0 years, 517 fatal and non-fatal cardiovascular events were registered (199 in women and 318 in men). The adjusted risk of cardiovascular events was lower in women (0.73, 0.60-0.89, P = 0.002) than in men; however, the cardiovascular risk advantage of women progressively diminished as SBP (as continuous variable) increased (P for interaction = 0.021; Figure 1). Similar results were obtained when considering SBP categories; when compared to men, women had a lower cardiovascular risk for SBP &amp;lt;130 mmHg (0.50, 0.31-0.80; P = 0.004) and between 130–140 mmHg (0.72, 0.53-0.99; P = 0.038), while no difference was observed for SBP&amp;gt;140 mmHg (0.85, 0.64-1.11; P = 0.232). Conclusion Higher BP levels abolish the cardiovascular protection seen in female vs male patients with overt CKD. This finding supports the need for higher awareness of hypertensive burden in women with CKD.

#4476 PRIMARY GLOMERULAR DISEASES AND LONG-TERM RISKS OF CKD PROGRESSION, CARDIOVASCULAR EVENTS AND DEATH: A SWEDISH NATIONWIDE COHORT STUDY

Abstract Background and Aims Although glomerular diseases are the third most frequent cause of end-stage kidney disease worldwide (after diabetes and hypertension), little is known about their long-term risks and complications. Method Using data from the Swedish Renal Registry (SRR-CKD) 2005-2021, we compared clinical outcomes between patients with the four most frequent primary glomerular diseases (IgA nephropathy [IgAN], focal segmental glomerulosclerosis [FSGS], minimal change disease [MCD] and membranous nephropathy [MN]) and patients with CKD attributed to non-inflammatory etiologies (i.e. without systemic auto-immune, inflammatory, infectious, hematologic malignancy, genetic disease, or polycystic kidney disease). Poisson models were used to estimate adjusted incidence rate ratios (IRR) of all-cause and cause-specific hospitalizations (cardiovascular-, acute kidney injury-, thromboembolism- and infection-related). Cox proportional hazards models were used to estimate adjusted hazard ratios (HR) of kidney replacement therapy (KRT), major adverse cardiovascular events (MACE) and death. Results We identified 2967 patients with primary glomerular disease (71% men, age 57 years, eGFR 28 mL/min/1.73 m2, uACR 63 mg/mmol) and 40026 patients with a non-inflammatory CKD (64% men, age 74 years, eGFR 22 mL/min/1.73 m2, uACR 20 mg/mmol). As compared to non-inflammatory CKD, patients with primary glomerular diseases were younger, had a lower prevalence of cardiovascular disease, higher eGFR but higher albuminuria. Over median follow-up of 6.3 [3.3;9.9] years, there were median 3.0 [1.0;7.0] hospitalizations per patient, 9890 (23%) KRT, 11708 (27%) MACE, and 21091 (49%) deaths. As compared to non-inflammatory CKD, patients with primary glomerular disease had a lower risk of all-cause (IRR 0.77 [0.75;0.79]), and all cause-specific hospitalizations, MACE (HR 0.56 [0.50;0.63]) and death (HR 0.57 [0.52;0.62], but a similar risk of KRT (HR 1.02 [0.95;1.10]) or AKI (HR 0.84 [0.70;1.02]) (Figure 1). Within primary glomerular diseases and as compared to IgAN, patients with FSGS had a higher risk of death (HR 1.29 [1.03;1.60]) and MACE (HR 1.49 [1.12;1.97]), and patients with MN and MCD had a lower risk of KRT. Conclusion In this nationwide analysis of patients with advanced CKD undergoing nephrologist-care, those with primary glomerular disease have an observed lower risk of adverse clinical events compared to non-inflammatory CKD diseases. However, their risks of AKI or KRT are similar, emphasizing the need of adequate treatment strategies in this population. We speculate that the long-term continuous exposure to comorbidities like diabetes and hypertension in patients with non-inflammatory CKD might explain these differences. Within single primary glomerular disease etiologies, FSGS is associated with the highest risk of cardiovascular and fatal complications. The study received grant support from CSL Vifor.

Sex difference in cardiovascular risk in patients with chronic kidney disease: pooled analysis of four cohort studies.

Progression of chronic kidney disease (CKD) has proven to be faster in men than in women. Whether the same holds true for cardiovascular risk remains ill-defined. We conducted a pooled analysis of 4 cohort studies from 40 nephrology clinics in Italy including patients with CKD (estimated GFR<60ml/min/1.73m2 or higher if proteinuria>0.15g/day). The aim was to compare multivariable-adjusted risk (Hazard Ratio, 95% Confidence Interval) of a composite cardiovascular endpoint (cardiovascular death and non-fatal myocardial infarction, congestive heart failure, stroke, revascularization, peripheral vascular disease, and non-traumatic amputation) in women (n=1192) versus men (n=1635). At baseline, women had slightly higher systolic blood pressure (SBP) as compared with men (139±19vs 138±18mmHg, P=0.049), lower eGFR (33.4vs 35.7mL/min/1.73 m2, P=0.001) and lower urine protein excretion (0.30g/day vs 0.45g/day in men, P<0.001). Women did not differ from men in age and prevalence of diabetes while having a lower prevalence of cardiovascular disease, left ventricular hypertrophy and smoking habit. During a median follow-up of 4.0 years, 517 fatal and non-fatal cardiovascular events were registered (199 in women and 318 in men). The adjusted risk of cardiovascular events was lower in women (0.73, 0.60-0.89, P=0.002) than in men; however, the cardiovascular risk advantage of women progressively diminished as SBP (as continuous variable) increased (P for interaction=0.021). Similar results were obtained when considering SBP categories; when compared to men, women had lower cardiovascular risk for SBP <130mmHg (0.50, 0.31-0.80; P=0.004) and between 130-140mmHg (0.72, 0.53-0.99; P=0.038), while no difference was observed for SBP>140mmHg (0.85, 0.64-1.11; P=0.232). Higher BP levels abolish the cardiovascular protection seen in female vs male patients with overt CKD. This finding supports the need for higher awareness of hypertensive burden in women with CKD.

Chemical composition of olive oil – an essential component of the Mediterranean diet and its impact on human health

The Mediterranean diet is known for its many health benefits, including the low prevalence of cardiovascular disease, atherosclerosis, diabetes, obesity, and cancer. Olive oil is considered an essential component of the Mediterranean diet. The consumption of olive oil is associated with many beneficial effects on the human body, most of which are attributed to its phenol content, which varies between cultivars due to different processing and extraction procedures, with only 0.3-1.5% of phenols being transferred to the oil from the olive fruit. Many studies suggest that olive oil phenolic compounds have a protective role in preventing cardiovascular diseases, cancer, diabetes mellitus type 2, metabolic syndrome, obesity, inflammation, and neurodegenerative diseases. Additionally, recent epidemiological research has shown that regular olive oil consumption is associated with increased longevity. Keywords: olive oil, phenols, health benefits

A comparison of arteriovenous fistula failure between Malaysian and Australian and New Zealand participants enrolled in the FAVOURED trial.

To describe and compare de novo arteriovenous fistula (AVF) failure rates between Australia and New Zealand (ANZ), and Malaysia. AVFs are preferred for haemodialysis access but are limited by high rates of early failure. A post hoc analysis of 353 participants from ANZ and Malaysia included in the FAVOURED randomised-controlled trial undergoing de novo AVF surgery was performed. Composite AVF failure (thrombosis, abandonment, cannulation failure) and its individual components were compared between ANZ (n = 209) and Malaysian (n = 144) participants using logistic regression adjusted for patient- and potentially modifiable clinical factors. Participants' mean age was 55 ± 14.3 years and 64% were male. Compared with ANZ participants, Malaysian participants were younger with lower body mass index, higher prevalence of diabetes mellitus and lower prevalence of cardiovascular disease. AVF failure was less frequent in the Malaysian cohort (38% vs 54%; adjusted odds ratio (OR) 0.53, 95% confidence interval (CI) 0.31-0.93). This difference was driven by lower odds of cannulation failure (29% vs 47%, OR 0.45, 95% CI 0.25-0.80), while the odds of AVF thrombosis (17% vs 20%, OR 1.24, 95% CI 0.62-2.48) and abandonment (25% vs 23%, OR 1.17, 95% CI 0.62-2.16) were similar. The risk of AVF failure was significantly lower in Malaysia compared to ANZ and driven by a lower risk of cannulation failure. Differences in practice patterns, including patient selection, surgical techniques, anaesthesia or cannulation techniques may account for regional outcome differences and warrant further investigation.

Lowering of Sympathetic Burst Frequency in Post‐Pubertal Female but not Male Rats

INTROCardiovascular disease (CVD) leads to an overall reduction in the quality of life and is the leading cause of mortality in the United States. The risk of CVD increases with age; however, women of reproductive age have a lower CVD prevalence. CVD is associated with elevations in sympathetic nerve activity, which has been analyzed in humans by quantifying sympathetic burst frequency. Whether sympathetic burst frequencies are different between pre‐ and post‐pubertal males and females is unknown.PURPOSEThe purpose of this study was to analyze sympathetic burst frequencies for potential differences between male and female rats.HYPOTHESISWe hypothesized that resting sympathetic burst frequency would be lower in post‐pubertal females compared to age‐matched males. We also predicted lower burst frequency in post‐ versus pre‐pubescent females.METHODSWe analyzed splanchnic nerve (SSNA) recordings from Inactin‐anesthetized male and female Sprague‐Dawley rats at 4‐weeks (pre‐pubertal) and 8‐ and 16‐weeks (post‐pubertal) of age. Sympathetic bursts were obtained by rectifying and integrating raw SSNA. Burst frequency was calculated using the Peak Parameters extension in LabChart software.RESULTSBurst frequency was higher in 4‐week (n=8) and 8‐week (n=9) old female rats compared to 16‐week old (n=6) female rats (5.6+1.2; 4.8+0.4 and 2.4+0.3 Hz, p&lt;.001 and p=0.02, respectively). At 16 weeks of age, female rats also had a significantly lower burst frequency when compared to male rats (n=4) (2.4+0.3 vs, 4.8+0.4 Hz, respectively, p=0.01). Finally, there was no significant difference found in burst frequencies between male rats at any age (p&gt;0.05 for all), suggesting sex‐dependent differences in the development of sympathoexcitation.CONCLUSIONPreliminary results suggest that following the onset of puberty in female rats, sympathetic burst frequency decreases over time, changes not seen in age‐matched male rats. Given CVD is significantly lower in premenopausal women, lower sympathetic nerve activity as a result of puberty may provide a mechanistic basis by which decreased sympathetic burst frequency protects against CVD. Future experiments may be conducted to explore other burst characteristics (e.g. burst amplitude and width), and the role of specific female sex hormones, to further understand sex‐dependent development of CVD.

District Differences in the Measured Values of Arterial Stiffness in Japan.

Background: In Japan, district differences in the prevalence of cardiovascular disease (CVD) are well-known. This study examined district differences in Japan in measured values of arterial stiffness, an independent risk factor for CVD.Methods and Results: Local residents participating in health checkups conducted in the Wakayama (n=461) and Nagano (n=186) prefectures in 2018 were recruited to the study. Brachial-ankle pulse wave velocity (baPWV) was evaluated as an index of arterial stiffness. After multivariate adjustment, baPWV was significantly higher in the Wakayama than Nagano district in subjects aged ≥70 years (mean [±SE] 1,912±25 vs. 1,763±30 cm/s; P<0.01), but not in subjects aged <70 years. Multivariate linear regression analysis demonstrated that the Wakayama/Nagano district difference was significantly (P<0.01) associated with baPWV.Conclusions: District differences were observed in the measured values of arterial stiffness in Wakayama and Nagano. The Wakayama and Nagano prefectures are representative areas with a relatively high and relatively low prevalence of CVD, respectively, in Japan. Therefore, based on the results of the present study, we propose to conduct a study to examine whether district differences in arterial stiffness underlie district differences in the prevalence of CVD.

The effect of entrance flow development on vortex formation and wall shear stress in a curved artery model

We numerically investigate the effect of entrance condition on the spatial and temporal evolution of multiple three-dimensional vortex pairs and the wall shear stress distribution in a curved artery model. We perform this study using a Newtonian blood-analog fluid subjected to a pulsatile flow with two inflow conditions. The first flow condition is fully developed while the second condition is undeveloped (i.e., uniform). We discuss the connection along the axial direction between regions of organized vorticity observed at various cross sections of the model and compare results between the different entrance conditions. We model a human artery with a simple, rigid 180° curved pipe with a circular cross section and constant curvature, neglecting the effects of taper, torsion, and elasticity. Numerical results are computed from a discontinuous high-order spectral element flow solver. The flow rate used in this study is physiological. We observe differences in secondary flow patterns, especially during the deceleration phase of the physiological waveform where multiple vortical structures of both Dean-type and Lyne-type coexist. The results indicate that decreased axial velocities under an undeveloped condition produce smaller secondary flows that ultimately inhibit growth of any interior flow vortices. We highlight the effect of the entrance condition on the formation of these structures and subsequent appearance of abnormal inner wall shear stresses, which suggest there may be a lower prevalence of cardiovascular disease in curved arteries where the flow is rather undeveloped—a potentially physiologically significant result to help understand the influence of blood flow development on disease.

Effects of Hydroxychloroquine on endOthelial function in eLDerly with sleep apnea (HOLD): study protocol for a randomized clinical trial

BackgroundSleep apnea and coronary artery disease are prevalent and relevant diseases. The mechanism by which sleep apnea leads to coronary artery disease remains unclear. Intermittent hypoxia, caused by sleep apnea, leads to inflammation and consequent endothelial dysfunction. Endothelial dysfunction precedes the development of atherosclerotic disease and the occurrence of cardiovascular events. Agents that potentially act to improve endothelial function can help prevent cardiovascular events. Patients using immunomodulators due to rheumatic diseases have a lower prevalence of cardiovascular diseases. However, the potential cardioprotective effect of these drugs in patients without autoimmune diseases is not clear. Hydroxychloroquine (HCQ) is an immunomodulator used to treat rheumatoid arthritis and systemic lupus erythematosus. In addition to its anti-inflammatory properties, HCQ reduces cholesterol and blood glucose levels and has antithrombotic effects. The drug is inexpensive and widely available. Adverse effects of HCQ are rare and occur more frequently with high doses.ObjectiveIn this randomized clinical trial, the effect of HCQ treatment on endothelial function will be tested in seniors with sleep apnea.MethodsWe will recruit participants over the age of 65 and with moderate-severe sleep apnea from an ongoing cohort. We chose to use this sample already evaluated for sleep apnea for reasons of convenience, but also because the elderly with sleep apnea are vulnerable to heart disease. Endothelial function will be assessed by examining flow-mediated dilation of the brachial artery, the gold standard method, considered an independent predictor of cardiovascular events in the general population and by peripheral arterial tonometry, the most recent and most easily obtained method. Hydroxychloroquine will be used at a dose of 400 mg/daily for 8 weeks.DiscussionOur study aims to obtain evidence, albeit preliminary, of the efficacy of hydroxychloroquine in improving endothelial function and reducing cardiovascular risk markers. If the improvement occurs, we plan to design a randomized multicenter clinical trial to confirm the findings.Trial registrationClinicalTrials.gov NCT04161339. Registered on November 2019.

Coronavirus disease 2019 in patients with cardiovascular disease: clinical features and implications on cardiac biomarkers assessment.

Previous cardiovascular disease (CVD) and myocardial involvement are common in coronavirus disease-19 (COVID-19). We investigated relationships between CVD, cardiac biomarkers and outcome in COVID-19. We analyzed n = 252 patients from a multicenter study and provided comparison according to the presence or absence of underlying CVD. Cardiac biomarkers high-sensitivity Troponin [upper reference of normality (URN) 35 pg/ml for Troponin I and 14 pg/ml for Troponin T] and natriuretic peptides (Nt-pro-B-type natriuretic peptide, URN 300 pg/ml and B-type natriuretic peptide, URN 100 pg/ml) were both available in n = 136. Mean age was 69 ± 16 years (56% men, 31% with previous CVD). Raised hs-Troponin and natriuretic peptides were detected in 36 and 50% of the cases respectively. Age, chronic obstructive pulmonary disease, hemoglobin, hs-Troponin and natriuretic peptides were independently associated with underlying CVD (P < 0.05 for all). Compared with the normal biomarkers subgroups, patients with isolated hs-Troponin elevation had higher in-hospital mortality (31 vs. 4%, P < 0.05), similar CVD prevalence (15 vs. 11%) and trend towards higher D-dimer (930 vs. 397 ng/ml, P = 0.140). Patients with both biomarkers elevated had higher age, D-dimer, CVD and in-hospital mortality prevalence compared with other subgroups (all P < 0.05 for trend). Outcome analysis revealed previous CVD [model 1: OR 2.72 (95% CI 1.14-6.49), P = 0.024. model 2: OR 2.65 (95% CI 1.05-6.71), P = 0.039], hs-Troponin (log10) [OR 2.61 (95% CI 1.21-5.66), P = 0.015] and natriuretic peptides (log10) [OR 5.84 (95%CI 2.43-14), P < 0.001] to be independently associated with in-hospital mortality. In our population, previous CVD was part of a vulnerable phenotype including older age, comorbidities, increased cardiac biomarkers and worse prognosis. Patients with isolated increase in hs-Troponin suffered higher mortality rates despite low prevalence of CVD, possibly explained by higher COVID-19-related systemic involvement.

Conversion from Aranesp® to NESP® in dialysis patients-Exploration of dosing strategies and the feasibility of extending the dosing interval.

Darbepoetin alpha is available as Aranesp® and NESP®, which differ in the inactive component and maximum dose-strength of prefilled syringes. We conducted an observational cohort study to investigate optimal conversion strategies and the feasibility of extending dosing intervals with higher-dose preparations in dialysis patients converting from Aranesp® to NESP®. Adult dialysis patients on Aranesp® with stable haemoglobin of 9-12 g/dL were converted to NESP® at the same monthly total dose according to one of three conversion regimens. Group A included patients on ≤80 mcg/month of Aranesp® who converted with dosing regimen unchanged. Group B patients converted to NESP® with extended dosing intervals using higher individual dose preparations. Group C were patients on 100 mcg Aranesp® who converted to NESP® 120 mcg with extended dosing intervals. Patients were observed for 6months. Fifty patients were included. All 24 Group A patients maintained stable haemoglobin. In Group B, 10 patients (50%) maintained stable haemoglobin with extension of dosing interval from 1.04 ± 0.14 to 3.03 ± 1.28 weeks. Factors associated with success in extending dosing interval included a lower prevalence of cardiovascular disease and a higher Kt/Vurea in peritoneal dialysis patients. Four patients (80%) in Group C maintained stable haemoglobin after conversion to NESP® 120 mcg with extended dosing interval. The use of NESP® 120 mcg was well tolerated, and was associated with reduced patient-reported pain score and 38% reduction of drug cost. Dialysis patients on Aranesp® can be successfully converted to NESP® and the dosing interval can be extended successfully in a significant proportion of patients, which could reduce discomfort and drug cost.

Formulation of Coated Tablets Film of Jengkol Fruit Seeds (Pithecellobium lobatum Benth.) as A Selenium Herbal Supplement

The correlation between the high content of selenium (Se) in plasma and the low prevalence of cardiovascular disease has been published in previous epidemiological studies. The content of Se in the plasma is determined by daily intake. A preliminary surveillance of Se content of several plants showed that the seeds of jengkol (Pithecellobium lobatum Benth.) has the highest concentration of Se. This study aims to develop a pharmaceutical formulation of Se supplement for adjuvant therapy of cardiovascular disease. The jengkol seeds was made into film coated tablets with a wet granulation method. Optimization of the core tablet formula was carried out with variations of binder concentration and coating material. Evaluation was carried out on uniformity of size and weight, disintegration time, hardness and friability. The content evaluation was carried out including the levels of Se, water content, ash, fat, protein, carbohydrate and crude fiber. The results showed that the F3 had the lowest friability and highest hardness. The coating of tablets using PVA has covered the smell of jengkol seed. The evaluation results showed that film coated tablets contained the Se level content of 0.074 ± 0.004 µg/g, water content of 2.19%, ash content of 1.88%, fat content of 0.89%, protein content of 0.66%, carbohydrate content of 94.38% and crude fiber content 1.79%. The results showed that the jengkol seed film coated tablet formulation could be used as a supplement in additional therapy for cardiovascular disease.Keywords : Pithecellobium lobatum, film coated tablet, herbal supplement, selenium

Keep Them in the Game: Screening for Cardiovascular Disease and Diabetes in Aging Athletes

Purpose: This observational cross-sectional study of aging athletes aims to (1) compare the prevalence of cardiovascular disease (CVD) and diabetes in aging athletes to the general population, (2) describe anthropometric values of aging athletes, (3) investigate the influence of cardiovascular sport competition on these measures, and (4) address any predictive value of evaluated measures. Methods: Health and sport history, blood pressure, waist circumference (WC), waist-to-hip ratio, and body mass index (BMI) were collected on 2351 aging athletes. Results: Aging athletes showed a significantly lower prevalence of CVD and diabetes than the general population. Athletes demonstrated BMI in the overweight range, WC in a healthy range, and waist-to-hip ratio in a healthy range for women but just over risk thresholds for men. Average blood pressure was near stage 1 hypertension. Waist circumference and waist-to-hip ratio were superior predictors of disease in the population. Cardiovascular athletes showed a lower disease risk and overall superior anthropometric values than other aging athletes. Conclusion: Aging athletes demonstrate a relatively low prevalence of CVD and diabetes despite demonstrating some anthropometric measurements over risk thresholds. Measures of central adiposity seem best for predicting disease in this population.

Association Between Residential Greenness, Cardiometabolic Disorders, and Cardiovascular Disease Among Adults in China

Living in areas with more vegetation (referred to as residential greenness) may be associated with cardiovascular disease (CVD), but little data are available from low- and middle-income countries. In addition, it remains unclear whether the presence of cardiometabolic disorders modifies or mediates the association between residential greenness and CVD. To evaluate the associations between residential greenness, cardiometabolic disorders, and CVD prevalence among adults in China. This analysis was performed as part of the 33 Communities Chinese Health Study, a large population-based cross-sectional study that was conducted in 33 communities (ranging from 0.25-0.64 km2) in 3 cities within the Liaoning province of northeastern China between April 1 and December 31, 2009. Participants included adults aged 18 to 74 years who had resided in the study area for 5 years or more. Greenness levels surrounding each participant's residential community were assessed using the normalized difference vegetation index and the soil-adjusted vegetation index from 2010. Lifetime CVD status (including myocardial infarction, heart failure, coronary heart disease, cerebral thrombosis, cerebral hemorrhage, cerebral embolism, and subarachnoid hemorrhage) was defined as a self-report of a physician diagnosis of CVD at the time of the survey. Cardiometabolic disorders, including hypertension, diabetes, dyslipidemia, and overweight or obese status, were measured and defined clinically. Generalized linear mixed models were used to evaluate the association between residential greenness levels and CVD prevalence. A 3-way decomposition method was used to explore whether the presence of cardiometabolic disorders mediated or modified the association between residential greenness and CVD. Data were analyzed from October 10 to May 30, 2020. Lifetime CVD status, the presence of cardiometabolic disorders, and residential greenness level. Among 24 845 participants, the mean (SD) age was 45.6 (13.3) years, and 12 661 participants (51.0%) were men. A total of 1006 participants (4.1%) reported having a diagnosis of CVD. An interquartile range (1-IQR) increase in the normalized difference vegetation index within 500 m of a community was associated with a 27% lower likelihood (odds ratio [OR], 0.73; 95% CI, 0.65-0.83; P < .001) of CVD prevalence, and an IQR increase in the soil-adjusted vegetation index within 500 m of a community was associated with a 26% lower likelihood (OR, 0.74; 95% CI, 0.66-0.84; P < .001) of CVD prevalence. The presence of cardiometabolic disorders was found to mediate the association between residential greenness and CVD, with mediation effects of 4.5% for hypertension, 4.1% for type 2 diabetes, 3.1% for overweight or obese status, 12.7% for hypercholesterolemia, 8.7% for hypertriglyceridemia, and 11.1% for high low-density lipoprotein cholesterol levels. In this cross-sectional study, higher residential greenness levels were associated with lower CVD prevalence, and this association may be partially mediated by the presence of cardiometabolic disorders. Further studies, preferably longitudinal, are warranted to confirm these findings.

Ethnic Disparities in Atherosclerotic Cardiovascular Disease Incidence and Prevalence Among Rheumatoid Arthritis Patients in the United States: a Systematic Review.

ObjectiveRheumatoid arthritis (RA) is associated with increased atherosclerotic cardiovascular disease (ASCVD). General population cohorts have shown African American individuals to have greater and Hispanic Americans to have lower cardiovascular disease prevalence when compared with non‐Hispanic white individuals; however, the reasons for these findings are not clear. This systematic review seeks to describe the incidence and prevalence of ASCVD stratified by race/ethnicity within the US RA population.MethodsMEDLINE, Embase, and Cochrane databases were searched for studies that reported incidence or prevalence of ASCVD (including, but not limited to, fatal and nonfatal stroke, myocardial infarction, and cardiovascular death) in those with RA. s and full texts were screened separately for inclusion by two reviewers, with a third reviewer to resolve discrepancies.ResultsWe screened 2625 abstracts and fully reviewed 138 manuscripts. Twenty‐one were included that cited at a minimum the percentage of non‐Hispanic whites in their population. No publication meeting entry criteria initially stratified ASCVD by race/ethnicity. The average prevalent ASCVD in RA is 46.9% (95% CI: 46.8–47) (range of prevalent ASCVD: 30%‐47%). The average incident ASCVD is 8.2% (95% CI: 8.14–8.25) (range of incident ASCVD 1%–46%).ConclusionIn this systematic review, we found a paucity of data on racially/ethnically diverse RA patients and ASCVD outcomes. Future studies should report the prevalence of ASCVD in various races/ethnicities with RA in the United States. These data would help inform clinicians on how best to manage cardiovascular disease risk in RA.

The haemochromatosis gene Hfe and Kupffer cells control LDL cholesterol homeostasis and impact on atherosclerosis development.

Imbalances of iron metabolism have been linked to the development of atherosclerosis. However, subjects with hereditary haemochromatosis have a lower prevalence of cardiovascular disease. The aim of our study was to understand the underlying mechanisms by combining data from genome-wide association study analyses in humans, CRISPR/Cas9 genome editing, and loss-of-function studies in mice. Our analysis of the Global Lipids Genetics Consortium (GLGC) dataset revealed that single nucleotide polymorphisms (SNPs) in the haemochromatosis gene HFE associate with reduced low-density lipoprotein cholesterol (LDL-C) in human plasma. The LDL-C lowering effect could be phenocopied in dyslipidaemic ApoE-/- mice lacking Hfe, which translated into reduced atherosclerosis burden. Mechanistically, we identified HFE as a negative regulator of LDL receptor expression in hepatocytes. Moreover, we uncovered liver-resident Kupffer cells (KCs) as central players in cholesterol homeostasis as they were found to acquire and transfer LDL-derived cholesterol to hepatocytes in an Abca1-dependent fashion, which is controlled by iron availability. Our results disentangle novel regulatory interactions between iron metabolism, KC biology and cholesterol homeostasis which are promising targets for treating dyslipidaemia but also provide a mechanistic explanation for reduced cardiovascular morbidity in subjects with haemochromatosis.

Patient-reported GP health assessments rather than individual cardiovascular risk burden are associated with the engagement in lifestyle changes: population-based survey in South Australia

BackgroundLittle is known about whether a more comprehensive health assessment, performed by a general practitioner (GP) during a clinical encounter, could influence patients’ lifestyle. We aimed to investigate whether health assessments, performed by GPs, are more important than the presence of cardiovascular disease (CVD) or cardiometabolic risk factors (obesity, diabetes, hypertension, dyslipidaemia) for engagement in lifestyle change.MethodsCross-sectional, population-based survey conducted in South Australia (September–December 2017) using face-to-face interviews and self-reported data of 2977 individuals aged 15+ years. The main outcome was engagement in four lifestyle changes: 1) increasing fruit/vegetable intake, 2) increasing physical activity level, 3) reducing alcohol consumption, and 4) attempts to stop smoking. Health assessments performed by a GP in the last 12 months included clinical/laboratory investigations (weight/waist circumference, blood pressure, glucose levels, lipid levels) and questions about lifestyle/wellbeing (current diet, physical activity, smoking status, alcohol intake, mental health, sleeping problems). Results were restricted to individuals aged 35+ years because of the low prevalence of CVD or their risk factors among younger participants. Logistic regression was used in all associations, adjusted for sociodemographic, lifestyle, mental health, and clinical variables.ResultsOf the 2384 investigated adults (mean age 57.3 ± 13.9 years; 51.9% females), 10.2% had CVD and 49.1% at least one cardiometabolic risk factor. Clinical/laboratory assessments performed by the GP were 2–3 times more frequent than assessments of lifestyle, mental health status, or sleeping problems, especially among those with CVD. Individuals with CVD or a cardiometabolic risk factor were no more likely to be increasing their fruit/vegetable consumption (33.6%), physical activity level (40.9%), reducing alcohol consumption (31.1%), or trying to quit smoking (34.0%) than ‘healthy’ participants. However, lifestyle changes were between 30 and 100% more likely when GPs performed three or more health assessments (either clinical/laboratory or questions about lifestyle/wellbeing) than when individuals did not visit the GP or when GPs performed no any assessment during these clinical encounters (p < 0.05 in all cases).ConclusionMore frequent and comprehensive CVD-related assessments by GPs were more important in promoting a healthier lifestyle than the presence of CVD or cardiometabolic risk factors by themselves.