Risk Factor For Cardiovascular Morbidity Research Articles

Dendritic Cell Epithelial Sodium Channel in Inflammation, Salt-Sensitive Hypertension, and Kidney Damage.

Salt-sensitive hypertension is a major risk factor for cardiovascular morbidity and mortality. The pathophysiologic mechanisms leading to different individual BP responses to changes in dietary salt remain elusive. Research in the last two decades revealed that the immune system plays a critical role in the development of hypertension and related end organ damage. Moreover, sodium accumulates nonosmotically in human tissue, including the skin and muscle, shifting the dogma on body sodium balance and its regulation. Emerging evidence suggests that high concentrations of extracellular sodium can directly trigger an inflammatory response in antigen-presenting cells (APCs), leading to hypertension and vascular and renal injury. Importantly, sodium entry into APCs is mediated by the epithelial sodium channel (ENaC). Although the role of the ENaC in renal regulation of sodium excretion and BP is well established, these new findings imply that the ENaC may also exert BP modulatory effects in extrarenal tissue through an immune-dependent pathway. In this review, we discuss the recent advances in our understanding of the pathophysiology of salt-sensitive hypertension with a particular focus on the roles of APCs and the extrarenal ENaC.

Reference Interval for Serum L-Homoarginine Determined with Enzyme-Linked Immunosorbent Assay in the Population-Based Study of Health in Pomerania.

Low levels of the endogenous amino acid L-homoarginine are a risk factor for cardiovascular morbidity and mortality. For individual risk prediction, commercially available test systems are mandatory. This study aims at formulating sex- and age-specific reference intervals of serum L-homoarginine determined with an ELISA. We determined reference intervals for serum L-homoarginine stratified by age and sex in a sample of 1285 healthy participants of the Study of Health in Pomerania (SHIP)-TREND cohort after exclusion of participants with cardiovascular diseases, diabetes mellitus, hypertension, metabolic syndrome, elevated liver enzymes, chronic kidney disease stages III or IV, or body mass index >25 kg/m2. Serum L-homoarginine was determined applying a commercially available ELISA. The reference cohort included 836 women (median age 41, 25th and 75th percentiles are 32 and 50 years) and 449 men (median age 38, 25th, and 75th percentiles are 30 and 49 years). The median serum concentration of L-homoarginine was 1.93 (25th 1.49; 75th 2.60) µmol/L in women and 2.02 (25th 1.63; 75th 2.61) µmol/L in men (P = 0.04). The reference intervals (2.5th to 97.5th percentile) were 0.89-5.29 µmol/L for women and 1.09-3.76 µmol/L for men. The L-homoarginine serum concentration declined over age decades in both sexes and a notable interaction with sex hormone intake in women was observed. The novelty of our study is that we determined reference intervals specific for the L-isomer being lower than those previously reported for homoarginine in SHIP and thus might be helpful in identifying individuals suitable for oral L-homoarginine supplementation.

Considerations for Optimal Blood Pressure Target of Hypertension

Hypertension is a major risk factor for cardiovascular morbidity and mortality that has led to a huge public health burden. The optimal target of blood pressure (BP) to prevent cardiovascular complications remains unclear. Based on the results of the Systolic BP Intervention Trial (SPRINT) in 2015, the 2017 American College of Cardiology/American Heart Association guidelines for diagnosis and management of high BP in adults has changed the diagnostic threshold from 140/90 to 130/80 mmHg, and the target BP to 130/80 mmHg for nearly all hypertensive patients diagnosed using the new criteria. However, the findings from the SPRINT trial were to an extent contrasting with the results of previous large randomized controlled trials, namely Action to Control Cardiovascular Risk in Diabetes (ACCORD) and Secondary Prevention of Small Subcortical Strokes (SPS3). Besides, the 2018 European Society of Cardiology/European Society of Hypertension guidelines and the 2018 Chinese guidelines have maintained the conventional threshold and recommended target of 140/90 mmHg for most hypertensive patients. Given the special measurement of BP in the SPRINT trial and using an automated measurement system, the intensive systolic BP target of 120 mmHg provided by the SPRINT trial was not widely adopted. Most recently, the Strategy of BP Intervention in the Elderly Hypertensive Patients (STEP) trial, with a higher systolic BP target of 110 to 130 mmHg in the intensive group, confirmed the benefit and safety of intensive BP control in patients with hypertension, in accordance with the SPRINT trial. Here, the results from randomized controlled trials, meta-analyses, and other observational research studies, have been reviewed to evaluate the optimal target of BP treatment and the threshold of diagnostic criteria for hypertension.

Distinct role of mitochondrial function and protein kinase C in intimal and medial calcification in vitro.

IntroductionVascular calcification (VC) is a major risk factor for cardiovascular morbidity and mortality. Depending on the location of mineral deposition within the arterial wall, VC is classified as intimal and medial calcification. Using in vitro mineralization assays, we developed protocols triggering both types of calcification in vascular smooth muscle cells (SMCs) following diverging molecular pathways.Materials and methods and resultsHuman coronary artery SMCs were cultured in osteogenic medium (OM) or high calcium phosphate medium (CaP) to induce a mineralized extracellular matrix. OM induces osteoblast-like differentiation of SMCs–a key process in intimal calcification during atherosclerotic plaque remodeling. CaP mimics hyperphosphatemia, associated with chronic kidney disease–a risk factor for medial calcification. Transcriptomic analysis revealed distinct gene expression profiles of OM and CaP-calcifying SMCs. OM and CaP-treated SMCs shared 107 differentially regulated genes related to SMC contraction and metabolism. Real-time extracellular efflux analysis demonstrated decreased mitochondrial respiration and glycolysis in CaP-treated SMCs compared to increased mitochondrial respiration without altered glycolysis in OM-treated SMCs. Subsequent kinome and in silico drug repurposing analysis (Connectivity Map) suggested a distinct role of protein kinase C (PKC). In vitro validation experiments demonstrated that the PKC activators prostratin and ingenol reduced calcification triggered by OM and promoted calcification triggered by CaP.ConclusionOur direct comparison results of two in vitro calcification models strengthen previous observations of distinct intracellular mechanisms that trigger OM and CaP-induced SMC calcification in vitro. We found a differential role of PKC in OM and CaP-calcified SMCs providing new potential cellular and molecular targets for pharmacological intervention in VC. Our data suggest that the field should limit the generalization of results found in in vitro studies using different calcification protocols.

Additive Effects of Diaphragmatic Breathing on Galvanic Skin Response, Blood Pressure, Pulmonary Function Test in Persons with Essential Hypertension

Introduction: Hypertension known as a raised arterial pressure. It is a major risk factor for cardiovascular morbidity and mortality. Stress is one of the factors that is responsible for hypertension which is measured by galvanic skin response (GSR). Findings from the previous studies were showed that the breathing exercise can help in the reduction of the blood pressure by acting on autonomic nervous system. Several studies have shown the effects of aerobic exercise in reduction of the blood pressure but there was scarcity of the studies done on additive effects of diaphragmatic breathing on essential hypertension. Materials and Method: After taking informed written consent subjects were randomly divided into two groups by simple random sampling method. Group A received Aerobic exercise and Group-B received Diaphragmatic breathing + Aerobic exercise. The duration of the treatment was of the 4 weeks. Pre and post intervention BP, GSR, FVC, FEV1 and DASS 21 were measured. Results: Paired t test and Wilcoxon signed rank test were used for within group analysis which shows the significant improvement was found in both groups in all outcome measure. There was significant difference was found in between groups in FVC and FEV1 (p < 0.05). However there was no statistical significant difference was found in between groups in SBP, DBP, GSR and DASS-21(p > 0.05). Conclusion: Diaphragmatic breathing along with the aerobic exercise has significant effects on FVC and FEV1 however there were no additional significant effects found on BP, GSR and DASS-21. Keywords: Hypertension, Diaphragmatic breathing, Aerobic exercise, Blood pressure, Galvanic skin response, pulmonary function test

Elevated triglycerides and reduced high-density lipoprotein cholesterol are independently associated with the onset of advanced chronic kidney disease: a cohort study of 911,360 individuals from the United Kingdom

BackgroundIncreased total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and decreased high-density lipoprotein cholesterol (HDL-C) concentrations, are established risk factors for cardiovascular morbidity and mortality; but their impact on the risk of advanced chronic kidney disease (CKD) is unclear. This study evaluates the association between the different lipid profiles and the onset of advanced CKD using a general population sample.MethodsThis observational study used records of 911,360 individuals from the English Clinical Practice Research Datalink (from 2000 to 2014), linked to coded hospital discharges and mortality registrations. Cox models were used to examine the independent association between the equal quarters of TC, TG, LDL-C, and HDL-C and the risk of advanced CKD, after adjustment for sex and age, and potential effect mediators.ResultsDuring a median follow-up of 7.5 years, 11,825 individuals developed CKD stages 4–5. After adjustment for sex and age, the hazard ratios (HRs) and confidence intervals (CIs) for CKD stages 4–5 comparing the 4th vs. 1st quarters of TG and 1st vs. 4th quarters of HDL-C were 2.69 (95% CI, 2.49–2.90) and 2.61 (95% CI, 2.42–2.80), respectively. Additional adjustment for potential effect mediators reduced the HRs to 1.28 (95% CI, 1.15–1.43), and 1.27 (95% CI, 1.14–1.41), respectively. There was no evidence of fully adjusted associations with CKD stages 4–5 for levels of either TC or LDL-C.ConclusionsElevated TG and reduced HDL-C levels are independently associated with the onset of advanced CKD. Future studies, such as in basic science and randomized trials, are needed to understand whether associations between TG and HDL-C and the development of CKD are causal.

Use of low-dose quetiapine increases the risk of major adverse cardiovascular events: results from a nationwide active comparator-controlled cohort study.

At standard doses used for schizophrenia or bipolar disorder, quetiapine has been associated with weight gain and increased levels of triglycerides,to-tal cholesterol and low-density lipoprotein (LDL) cholesterol, which are risk factors for cardiovascular morbidity and mortality. However, this drug is also commonly used off-label at low doses for anxiolytic or hypnotic purposes, and its cardiovascular safety at these doses is unknown. We aimed to assess the risk of major adverse cardiovascular events with use of low-dose quetiapine compared to use of Z-drug hypnotics in a nationwide, active comparator-controlled cohort study. The cohort included new users of either drugs in Denmark from 2003 to 2017, aged 18-85 years, without history of ischemic stroke, myocardial infarction, cancer, and severe mental illness. The main outcome was the occurrence of major adverse cardiovascular events, defined as non-fatal myocardial infarction or ischemic stroke, or death from cardiovascular causes. Selective serotonin reuptake inhibitors (SSRIs) were used as an alternative comparator in sensitivity analyses. Altogether, we compared 60,566 low-dose quetiapine users with 454,567 Z-drug users, followed for 890,198 person-years in intent-to-treat analysis, and 330,334 person-years in as-treated analysis. In intention-to-treat analysis, low-dose quetiapine was associated with an increased risk of major adverse cardiovascular events (adjusted hazard ratio, aHR=1.13, 95% CI: 1.02-1.24, p=0.014) and cardiovascular death (aHR=1.26, 95% CI: 1.11-1.43, p<0.001). In as-treated analysis, continuous low-dose quetiapine use was associated with increased risk of major adverse cardiovascular events (aHR=1.52, 95% CI: 1.35-1.70, p<0.001), non-fatal ischemic stroke (aHR=1.37, 95% CI: 1.13-1.68, p=0.002) and cardiovascular death (aHR=1.90, 95% CI: 1.64-2.19, p<0.001). The risk of major adverse cardiovascular events was greater in women (aHR=1.28, p=0.02) and those aged ≥65 years at initiation (aHR=1.24, p<0.001). Compared to SSRIs, low-dose quetiapine use was associated with an increased risk of major adverse cardiovascular events (aHR=1.42, p<0.001), non-fatal ischemic stroke (aHR=1.27, p=0.0028) and cardiovascular death (aHR=1.72, p<0.001). So, we conclude that the use of low-dose quetiapine is associated with an increased risk of major adverse cardiovascular events, especially in women and the elderly. On the basis of these findings, we suggest that use of off-label low-dose quetiapine for sedative or hypnotic purposes should be discouraged.

Abstract P325: Visit-To-Visit Blood Pressure Variability Is A Major Risk Factor For Renal Outcomes In Hypertensive Patients: Evidence From The 20-Year Follow-Up Of The Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT)

Introduction: Observational studies showed that visit-to-visit blood pressure variability (BPV) is a significant independent risk factor for cardiovascular morbidity and all-cause mortality. However, the relation between BPV with renal outcomes remains controversial. Methods: In the ASCOT-Legacy Study, 7,092 hypertensive patients, aged 40-79 years, who had at least three other cardiovascular risk factors have been followed for up to 20 years to report the long-term determinants of renal outcomes. All available BP visit records (n=100,933) were included after excluding the first six months observations. The mean of systolic blood pressure (SBP) as a measure of BP control and the standard deviation (SD) of all SBPs as an estimate of visit-to-visit BPV were calculated for the five years of the trial. Participants were then followed for up to 15 years after the end of the trial using the UK National Health Service (NHS) electronic health records. Total renal outcomes (renal failure, chronic kidney disease, dialysis and transplantation) were measured using Cox proportional hazards model. Results: About one-third (n=2,354) of participants experienced at least one of the renal outcomes during the follow-up. Our findings showed that an increase per one SD (10.39 mmHg) in mean SBP was associated with a hazard ratio (HR) of 1.23 (95%CI 1.17-1.29; p&lt;0.001) and an increase per one SD (4.72 mmHg) in BPV was associated with an HR of 1.20 (95%CI 1.14-1.26; p&lt;0.001) for total renal outcomes. Likewise, BPV was associated with a higher risk of renal failure (1.19 [95%CI 1.13-1.26]; p&lt;0.001), chronic kidney disease (1.25 [95%CI 1.08-1.44]; p=0.002), and dialysis and transplantation (1.43 [95%CI 1.19-1.71]; p&lt;0.001) after adjusting for mean BP, number of visits and other confounding variables. Conclusions: Both mean SBP and BPV are strong predictors of long-term renal outcomes, but BPV, independent of mean BP, confers a significant additional risk and should be considered for future preventive and therapeutic strategies.

Sex differences of lipoprotein(a) levels and associated risk of morbidity and mortality by age: The Copenhagen general population study

Background and Aims : Lipoprotein(a) is a well-known causal risk factor for cardiovascular morbidity and mortality. Little is known about the effect of age and sex on lipoprotein(a) levels, and it is largely unknown if the same elevation in lipoprotein(a) confer the same increase in risk of morbidity and mortality in women and men. We hypothesized that lipoprotein(a) levels and lipoprotein(a) associated risk of morbidity and mortality by age are similar in women and men.

Effect of high-intensity aerobic exercise on serum uric acid in hypertension: compare with moderate-intensity aerobic exercise

Hypertension is one of the major risk factors for cardiovascular morbidity and morbidity since high blood pressure can cause damage to microvascular and macrovascular organs. The Sixty non-smoker participants were divided into two main groups. Thirty participants group with high-intensity aerobic exercise and a second thirty group with moderate-intensity aerobic exercise. The electrical treadmill exercise is used three times per week for eight for each 25-30 minutes. Peripheral arterial blood pressure measurements and blood investigation in the form of serum uric acid and renal function tests were tested for each participant. The resulting data showed a significantly decreased effect on both serum uric acid and renal function tests in high-intensity intervals and continuous moderate exercise with more improvement with continuous moderate exercise 16% in serum uric acid and 27.5 % in creatinine. In conclusion, moderate continuous exercise reduces serum uric acid and creatinine better than high-intensity interval exercise. Both have the same effect on blood pressure and urea, but moderate continuous exercise has a crystal-clear effect that cannot be denied.

Cross-Sectional Blood Metabolite Markers of Hypertension: A Multicohort Analysis of 44,306 Individuals from the COnsortium of METabolomics Studies.

Hypertension is the main modifiable risk factor for cardiovascular morbidity and mortality but discovering molecular mechanisms for targeted treatment has been challenging. Here we investigate associations of blood metabolite markers with hypertension by integrating data from nine intercontinental cohorts from the COnsortium of METabolomics Studies. We included 44,306 individuals with circulating metabolites (up to 813). Metabolites were aligned and inverse normalised to allow intra-platform comparison. Logistic models adjusting for covariates were performed in each cohort and results were combined using random-effect inverse-variance meta-analyses adjusting for multiple testing. We further conducted canonical pathway analysis to investigate the pathways underlying the hypertension-associated metabolites. In 12,479 hypertensive cases and 31,827 controls without renal impairment, we identified 38 metabolites, associated with hypertension after adjusting for age, sex, body mass index, ethnicity, and multiple testing. Of these, 32 metabolite associations, predominantly lipid (steroids and fatty acyls) and organic acids (amino-, hydroxy-, and keto-acids) remained after further adjusting for comorbidities and dietary intake. Among the identified metabolites, 5 were novel, including 2 bile acids, 2 glycerophospholipids, and ketoleucine. Pathway analysis further implicates the role of the amino-acids, serine/glycine, and bile acids in hypertension regulation. In the largest cross-sectional hypertension-metabolomics study to date, we identify 32 circulating metabolites (of which 5 novel and 27 confirmed) that are potentially actionable targets for intervention. Further in-vivo studies are needed to identify their specific role in the aetiology or progression of hypertension.

Sex differences of lipoprotein(a) levels and associated risk of morbidity and mortality by age: The Copenhagen General Population Study

Background and aimsLipoprotein(a) is a well-known causal risk factor for cardiovascular morbidity and mortality. Little is known about the effect of age and sex on lipoprotein(a) levels, and it is largely unknown if the same elevation in lipoprotein(a) confers the same increase in risk in women and men. We investigated whether lipoprotein(a) levels and lipoprotein(a) associated risks of morbidity and mortality by age are similar in women and men. MethodsWe included 37,545 women and 32,497 men from the Copenhagen General Population Study. ResultsPlasma lipoprotein(a) increased with age, and in women we found an additional increase around age 50 (age by sex interaction p = 8∙10−7). In women, levels were 27% higher after menopause (p = 4∙10−61) and 12% lower during hormone replacement therapy (p = 2∙10−19). Adjustment for estimated Glomerular Filtration Rate in both sexes and plasma estradiol in women resulted in attenuated sex differences in lipoprotein(a) levels. In sex and age stratified multivariable adjusted models, lipoprotein(a) >40 mg/dL(83 nmol/L) versus <10 mg/dL(18 nmol/L) was associated with increased risk of myocardial infarction, ischemic heart disease, aortic valve stenosis, and heart failure (men only), but not statistically significant with risk of ischemic stroke, cardiovascular mortality, or all-cause mortality. ConclusionsLipoprotein(a) levels increased modestly around age 50 selectively in women; however, risk of morbidity and mortality for high lipoprotein(a) was similar in women and men above age 50. This implies that elevated lipoprotein(a) above age 50 is a relatively more common cardiovascular risk factor in women, pointing toward repeat measurements in women above age 50.

Terapia Hormonal e Hipertensão em Mulheres na Pós-Menopausa: Resultados do Estudo Longitudinal de Saúde do Adulto (ELSA-Brasil)

ResumoFundamento A hipertensão arterial é considerada um importante fator de risco de morbidade e mortalidade cardiovascular em mulheres na pós-menopausa. Embora a terapia hormonal da menopausa (THM) seja um tratamento muito eficiente para sintomas vasomotores nesse período, a influência dessa terapia na pressão arterial ainda não está clara.Objetivo Avaliar a relação entre o uso de THM e a hipertensão em participantes do ELSA-Brasil.Métodos Um estudo transversal usando dados da linha de base da coorte ELSA-Brasil, com 2.138 mulheres que passaram por menopausa natural. Neste estudo, foi analisado a hipertensão, definida como pressão arterial ≥140/90 mmHg ou uso anterior de anti-hipertensivo, e o uso da THM, com participantes sendo classificadas em grupos daquelas que nunca usaram, que já usaram e que estavam em uso atual. As associações foram avaliadas usando-se um modelo de regressão logística multivariada com uma significância estatística definida em p<0,05.Resultados No total, 1.492 mulheres (69,8%) nunca tinham usado a THM, 457 (21,4%) tinham usado no passado, e 189 (8,8%) estavam em uso atual. O uso de THM foi mais comum em mulheres que tinham índice de massa corporal <25 kg/m2 e níveis de triglicérides <150 mg/dl, que eram fisicamente menos inativas, não fumantes e não diabéticas. As mulheres em uso atual da THM apresentaram menores chances de ter hipertensão (OR=0,59; IC 95%: 0,41-0,85), em comparação com as que nunca a usaram. Na maioria dos casos, a THM foi iniciada com idade até 59 anos, com menos de 10 anos de menopausa e o uso durou até cinco anos.Conclusão O uso atual da THM não esteve relacionado à hipertensão, especialmente em mulheres saudáveis e que tinham menos de 60 anos de idade.

MO195: Kidney Function and the Risk of Heart Failure Among Older Adults: A Prospective Population-Based Cohort Study

Abstract BACKGROUND AND AIMS Decreased kidney function is an established risk factor of cardiovascular morbidity including heart failure (HF) as well as cardiovascular and all-cause mortality among adults. However, the role of decreased kidney function with regard to these outcomes among old and very old adults remains poorly understood. This is an important knowledge gap given the common decline of kidney function in advanced age, which can affect both healthy individuals and patients with significant morbidity. To this end, we conducted a population-based study to assess whether decreased kidney function is associated with an increased risk of HF, cardiovascular and all-cause mortality in a prospective cohort of community-dwelling older adults. METHOD We included participants of the Berlin Initiative Study (BIS), age ≥70 years, with estimated glomerular filtration rate (eGFRBIS2) at baseline (between 2009 and 2011) and information on prior diagnosis of HF. Participants were followed from baseline until the occurrence of one of the study outcomes (see below) or December 2020, the latest date of data availability. Potential confounders included demographic characteristics, anthropometrics (body mass index), lifestyle factors (alcohol consumption, smoking, physical exercise), proxies of socioeconomic status (education, income), medications (major classes of antihypertensive drugs, oral anticoagulants, antiplatelet agents), and comorbidities measured at baseline using face-to-face interviews and administrative healthcare data. The three study outcomes were hospitalization for HF (HHF), cardiovascular death and all-cause mortality. HHF was defined based on inpatient diagnostic codes, and the mortality outcomes were defined based on a combination of administrative healthcare data, death certificates and hospital discharge notes. Cox proportional hazards models estimated hazard ratios (HRs) with 95% confidence intervals (CIs) of the three outcomes associated with decreased kidney function (eGFRBIS2 &amp;lt; 60 mL/min/1.73 m2) compared with retained kidney function (eGFRBIS2 ≥ 60 mL/min/1.73 m2). Analyses were repeated among BIS participants with prior HF. RESULTS Our study cohort included 1466 HF free older adults (mean age 79 years; 55% female). Compared with retained kidney function, decreased kidney function was associated with increased risks of HHF (crude incidence rates per 100/year: 2.7 versus 1.1; adjusted HR, 1.48; 95% CI, 1.06–2.07), cardiovascular death (crude incidence rates per 100/year: 2.7 versus 0.9; adjusted HR, 1.49; 95% CI, 1.06–2.09), and all-cause mortality (crude incidence rates per 100/year: 6.3 versus 2.8; adjusted HR, 1.27; 95% CI, 1.03–1.57). Kaplan-Meier curves for the three study outcomes are shown in Figure 1. Among the 590 older adults with prior HF (mean age 83 years; 54% female), the effect estimates were similar albeit less precise (HHF: HR, 1.32; 95% CI, 0.88–1.98/cardiovascular death: HR, 1.67; 95% CI, 1.06–2.63/all-cause mortality: HR, 1.22; 95% CI, 0.91–1.63). CONCLUSION Our population-based study showed that decreased kidney function is associated with increased risks of cardiovascular morbidity and cardiovascular and all-cause mortality among older adults, corroborating findings in younger populations.

MO188: Elevated Serum Soluble Urokinase-Type Plasminogen Activator Receptor Level is Linked to Aortic Stiffness in Chronic Haemodialysis Patients

Abstract BACKGROUND AND AIMS Soluble urokinase-type plasminogen activator receptor (suPAR) is associated with inflammation and contributing in the pathogenesis of atherosclerosis. Aortic stiffness is associated with aging-associated vascular diseases and is also an independent risk factor of cardiovascular morbidity and mortality. We evaluated the association between serum suPAR and aortic stiffness in patients with chronic haemodialysis (HD). METHOD A total of 135 patients with HD were enrolled in this study. Carotid–femoral pulse wave velocity (cfPWV) was measured using the SphygmoCor system. Patients with cfPWV &amp;gt;10 m/s were defined as the aortic stiffness group. Serum suPAR levels were measured using a commercial enzyme-linked immunosorbent assay kit. RESULTS Fifty-five HD patients (40.7%) had aortic stiffness and higher percentages of diabetes (P = .001), hypertension (P = .039), were of older age (P = .007) and had higher systolic blood pressure (P = .025), serum glucose level (P = .019), C-reactive protein (P = .039) and suPAR levels (P &amp;lt; .001) compared to control group. After adjusting for factors significantly associated with aortic stiffness by multivariate logistic regression analysis, serum suPAR [odds ratio (OR): 1.910, 95% confidence interval (CI): 1.485–2.458, P &amp;lt; .001] and age (OR: 1.040, 95% CI: 1.001–1.080, P = .048) were independently associated with aortic stiffness in patients with chronic HD. After multivariable forward stepwise linear regression analysis also noted that serum suPAR level (β = 0.442, adjusted R2 change = 0.250, P &amp;lt; .001) was positively associated with with cfPWV values in HD patients. CONCLUSION Serum suPAR level is positively associated with cfPWV values and is a biomarker for aortic stiffness in patients with chronic HD.

Development of a Portable Infrared-Type Noncontact Blood Pressure Measuring Device and Evaluation of Blood Pressure Elevation during Driving

Hypertension has been established as a major risk factor for cardiovascular morbidity and mortality. Therefore, prevention of hypertension is an urgent matter to maintain people’s health and avoid death, and out-of-office blood pressure measurement is said to be an integral part of the diagnosis and management of hypertension. Hypertension not only causes loss of productivity and economic loss but is also a major cause of road accidents. Therefore, it is important to develop an in-vehicle noncontact blood pressure measurement system for drivers. In addition to measurement accuracy, proper detection timing is also important, and there must be no difference between noncontact and contact detection times. In this study, we introduce an infrared cuffless and portable noncontact blood pressure monitoring system, its measurement principle, and performance evaluation. A total of 13 male adults participated in the experiment to evaluate the effect of time lag between the use of the infrared blood pressure monitoring system and the contact blood pressure monitoring system using a driving simulator. The changepoint method was applied to detect the first change point in the blood pressure time series data caused by the unexpected first appearance of the vehicle. The results showed that the detection time of the developed system was about 2.5 s shorter than that of the contact-type continuous blood pressure measurement system, with no significant difference.

Acute Cardiovascular Effects of Hydrotreated Vegetable Oil Exhaust.

Ambient air pollution is recognized as a key risk factor for cardiovascular morbidity and mortality contributing to the global disease burden. The use of renewable diesel fuels, such as hydrotreated vegetable oil (HVO), have increased in recent years and its impact on human health are not completely known. The present study investigated changes in cardiovascular tone in response to exposure to diluted HVO exhaust. The study participants, 19 healthy volunteers, were exposed in a chamber on four separate occasions for 3 h and in a randomized order to: (1) HVO exhaust from a wheel loader without exhaust aftertreatment, (2) HVO exhaust from a wheel loader with an aftertreatment system, (3) clean air enriched with dry NaCl salt particles, and (4) clean air. Synchronized electrocardiogram (ECG) and photoplethysmogram (PPG) signals were recorded throughout the exposure sessions. Pulse decomposition analysis (PDA) was applied to characterize PPG pulse morphology, and heart rate variability (HRV) indexes as well as pulse transit time (PTT) indexes were computed. Relative changes of PDA features, HRV features and PTT features at 1, 2, and 3 h after onset of the exposure was obtained for each participant and exposure session. The PDA index A13, reflecting vascular compliance, increased significantly in both HVO exposure sessions but not in the clean air or NaCl exposure sessions. However, the individual variation was large and the differences between exposure sessions were not statistically significant.

Abstract P111: Differentially Methylated DNA Regions In Left Ventricular Hypertrophy: A HyperGEN Study

Left ventricular (LV) hypertrophy (LVH) is an independent risk factor for cardiovascular morbidity and mortality that is commonly associated with hypertension. African Americans (AAs) experience an especially high risk of LVH. Genomic studies have identified potential candidate genes associated with LVH, but more research is needed to further explain the high estimated heritability for these traits in AAs. Epigenetic modifications, such as DNA methylation, may account for the unexplained heritability in LVH in AAs. In this study, we used epigenotype and echocardiography data from 636 African Americans selected from the Hypertension Genetic Epidemiology Network (HyperGEN) to identify differentially methylated regions (DMRs) of DNA in association with LV related traits. DNA was isolated from participants’ whole blood, and more than 485,000 CpGs were assayed on Illumina Methyl450K arrays. Linear mixed models were used to test the association between a DMR and LV trait using the coMethDMR package in R. We identified several DMRs associated with LV traits in HyperGEN. There was an association between methylation of XKR6 and ejection fraction (β[SE]:0.005[0.001], FDR: 0.056), as well as TRAK1 and LV internal diastolic dimension (β[SE]:0.113[0.027], FDR: 0.042). There was also an inverse relationship between LV mass indexed to height and methylation of GSE1 (β[SE]:-0.002[0.001], FDR: 0.085), RPS15A (β[SE]:-0.002[0.001], FDR: 0.085), and PSMD7 (β[SE]:-0.003[0.001], FDR: 0.085). Additionally, relative wall thickness was inversely associated with a DMR annotated to DNHD1 (β[SE]:-1.269[0.275], FDR: 0.008). Methylation variations of GSE1 , PSMD7 , and DNHD1 have previously been linked to cardiac structural function, and external validation of these findings is in progress. In summary, differentially methylated regions of DNA may help explain additional variation in LVH-related traits and heritability in AAs. Future studies should evaluate potential relationships between regional DNA methylation patterns and the development and progression of LVH.

Common carotid artery characteristics in patients with repaired aortic coarctation compared to other cardiovascular risk factors

AimsIncreased common carotid artery (CCA) intima media thickness (cIMT) is a well-known risk factor for cardiovascular morbidity and mortality. cIMT thickening has been described in patients with repaired aortic coarctation (CoA), but data on mechanism and clinical relevance in this population are scarce. Our aim was to gain mechanistic insights into cIMT thickening of patients with repaired CoA by comparing their wall architecture to patients with coronary artery disease (CAD), other congenital heart diseases (oCHD), and healthy controls. Methods and resultsA total of 310 subjects were included (CoA (n ​= ​58), oCHD (n ​= ​96), CAD (n ​= ​68) and healthy controls (n ​= ​88)). CIMT and lumen diameter (LD) were determined using semiautomated analysis software. Linear regression analyses were performed correcting for relevant covariates. While patients with repaired CoA and CAD both had significantly increased cIMT and cIMT/LD ratios, LD was increased only in CoA patients. Furthermore, patients with repaired CoA had decreased CCA stiffness. CCA characteristics in the oCHD group were not significantly different from controls. ConclusionThe mechanism of cIMT thickening in patients with repaired CoA may differ from CAD. While there is concentric remodeling in the latter, we see predominant eccentric remodeling in the CoA group, which could be due to increased flow as a result of compliance mismatch at the CoA repair site. We therefore suggest that the prognostic value of cIMT in post-CoA patients should be validated separately prior to using it to guide clinical management in this group.

Vascular Calcification in Chronic Kidney Disease: An Update and Perspective.

Chronic kidney disease is a devastating condition resulting from irreversible loss of nephron numbers and function and leading to end-stage renal disease and mineral disorders. Vascular calcification, an ectopic deposition of calcium-phosphate salts in blood vessel walls and heart valves, is an independent risk factor of cardiovascular morbidity and mortality in chronic kidney disease. Moreover, aging and related metabolic disorders are essential risk factors for chronic kidney disease and vascular calcification. Marked progress has been recently made in understanding and treating vascular calcification in chronic kidney disease. However, there is a paucity of systematic reviews summarizing this progress, and investigating unresolved issues is warranted. In this systematic review, we aimed to overview the underlying mechanisms of vascular calcification in chronic kidney diseases and discuss the impact of chronic kidney disease on the pathophysiology of vascular calcification. Additionally, we summarized potential clinical diagnostic biomarkers and therapeutic applications for vascular calcification with chronic kidney disease. This review may offer new insights into the pathogenesis, diagnosis, and therapeutic intervention of vascular calcification.