Risk Factor For Cardiovascular Morbidity Research Articles

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.

Does exercise stress testing carry an incremental prognostic value beyond resting office blood pressure?

Does exercise stress testing carry an incremental prognostic value beyond resting office blood pressure?

A Cross-sectional Study of the Epidemiological Characteristics of Hypertension in a Mass Screening of Adult Volunteers at the Renaissance University Hospital

<i>Introduction</i>: Hypertension is a major public health problem and an important area of research due to its high prevalence. It remains to be the leading cause of death globally and a major risk factor for cardiovascular morbidity and mortality associated with other complications. Its management is a major challenge in our society; the large disparities in the regional burden of hypertension are accompanied by low levels of awareness, treatment and control rates. The objective of this study was to determine the epidemiological characteristics of hypertension and its associated risk factors. This is a cross-sectional study conducted at the Renaissance University Hospital in June 2021 during a screening campaign and to raise awareness for hypertension. Its adult volunteers aged 18 years and older were present. The data was collected individually by interview using a collection form. <i>Results</i>: The sample consisted of 350 volunteers with 227 males (64.86%) with a sex ratio of 1.84. The mean standard deviation of total age was 38.96 (12.31) years. The prevalence of hypertension was present in 22.28% of participants (n=78). Male was predominant among hypertensive inviduals (65.38%) and the mean standard deviation age of hypertensives was 42.85 (13.42) years. Associated risk factors were predominantly hyperglycaemia; 26.9% of cases (n=94), alcohol consumption; 23.43% of cases (n=82) and obesity; 16% of cases (n=56). <i>Conclusion</i>: This study shows a high prevalence of hypertension and it concerns predominantly males. It affects young adults and the main associated cardiovascular risk factors were oage, obesity, alcohol consumption and hyperglycaemia.

Impact of Mobile Technology Solution on Self-Management in Patients with Hypertension: Advantages and Barriers

Hypertension is a major risk factor for cardiovascular morbidity and mortality. It is a condition that increases the high risk of heart, liver, and other diseases. Since hypertension is one of the biggest global public health issues, patients require more interventions to manage their blood pressure. The vast use of mobile phones and applications with medication features has turned a smartphone into a medical device. These tools are helpful for a physician in the treatment of hypertension. Mobile health applications are utilised to manage hypertension at the moment; however, there is a lack of information regarding their efficacy. Smartphones and their applications are evolving quickly hence the rise in the innovation of mobile health applications. Mobile-based applications are helpful in-patient education and reinforce the behaviour through constant reminders, medication, and appointment alarms. The main objective of this study is to determine the impact of mobile health applications on self-management in patients with hypertension and its advantages and disadvantages. We used publications from 2015 and later as a time frame and searched on the first five pages of Google Scholar, JSTOR, Hindawi, PubMed, and ResearchGate. We group all associated terms that might turn up articles on this subject in the search results. The total number of database records that we identified were 213, and the duplicate identified and removed were 117; hence the screened records were 96. The reports excluded based on abstract and title were 31. Articles with full text and have been accessed for final inclusion were 65. The excluded articles were 51, and the studies included in the qualitative analysis were 14.

The Effects of Single Pill Combinations on Adherence and Blood Pressure Control in Hypertensive Patients.

Background:Hypertension is the most important risk factor for cardiovascular morbidity and mortality. Blood pressure control rates are as low as 17% to 31% in patients diagnosed with hypertension in high-income countries; control rates are likely poorer in low- to middle- and low-income countries. Blood pressure control rates are as low as 17% to 31% in patients diagnosed with hypertension in high-income countries; control rates are likely poorer in low- to middle- and low- income countries. Overall, 43% to 66% of patients fail to adhere to their prescribed antihypertensive medications, and after 1 year, ≈40% of patients with hypertension may stop their initial drug treatment.Objective:The aim of the study was to evaluate the effects of single pill combination antihypertensive drugs on the adherence to treatment, blood pressure control and cardiovascular events vs. free-combination therapy.Methods:We enrolled 192 adult hypertensive patients not older than 79 years, with untreated or uncontrolled hypertension despite previously receiving free combination antihypertensive therapy, between November 2020 and March 2022. Patients treated with single pill combination (SPC) were compared with an arm of the same size (n = 96) and matched by age and gender who received a standard free combination (FC) antihypertensive therapy.Results:There were significant reductions from baseline to month 6 of follow-up in office SBP in the SPC group vs. reduction in FC group (21.9 vs. 13.1 mmHg; p < 0.0001). There were significant reductions from baseline to month 6 of follow-up in office DBP in the SPC group vs. group with free-combination therapy (13.7 vs. 8.0 mmHg; p < 0.0001). At 6 months, 94 participants (98%) were still prescribed the SPC therapy. At the final 6-month study visit, 84.2% of patients in the SPC therapy group were adherent to the prescribed antihypertensive therapy vs. 52% of patients in the FC group. Target BP values (mean 24h ambulatory systolic/diastolic BP < 130/80 mmHg) were reached by more recipients of SPC than free-combination therapy (78.2% vs. 46.3%, p < 0.05) at month 6 of follow-up.Conclusion:Treatment with single pill combinations (SPC), is the emerging best practice for safe, effective, rapid, and convenient hypertension control. It improves the affordability, adherence and control of arterial hypertension.

Salt-Sensitivity of Blood Pressure and Insulin Resistance.

Salt sensitivity of blood pressure (SSBP) is an independent risk factor for cardiovascular morbidity and mortality that is seen in both hypertensive and normotensive populations. Insulin resistance (IR) strongly correlates with SSBP and affects nearly 50% of salt sensitive people. While the precise mechanism by which IR and SSBP relate remains elusive, several common pathways are involved in the genesis of both processes, including vascular dysfunction and immune activation. Vascular dysfunction associated with insulin resistance is characterized by loss of nitric oxide (NO)-mediated vasodilation and heightened endothelin-1 induced vasoconstriction, as well as capillary rarefaction. It manifests with increased blood pressure (BP) in salt sensitive murine models. Another common denominator in the pathogenesis of insulin resistance, hypertension, and salt sensitivity (SS) is immune activation involving pro-inflammatory cytokines like tumor necrosis factor (TNF)-α, IL-1β, and IL-6. In the last decade, a new understanding of interstitial sodium storage in tissues such as skin and muscle has revolutionized traditional concepts of body sodium handling and pathogenesis of SS. We have shown that interstitial Na+ can trigger a T cell mediated inflammatory response through formation of isolevuglandin protein adducts in antigen presenting cells (APCs), and that this response is implicated in salt sensitive hypertension. The peroxisome proliferator-activated receptor γ (PPARγ) is a transcription factor that modulates both insulin sensitivity and BP. PPARγ agonists increase insulin sensitivity and ameliorate salt sensitivity, whereas deficiency of PPARγ results in severe insulin resistance and hypertension. These findings suggest that PPARγ plays a role in the common pathogenesis of insulin sensitivity and salt sensitivity, perhaps via effects on the immune system and vascular function. The goal of this review is to discuss those mechanisms that may play a role in both SSBP and in insulin resistance.

Lin11-Isl1-Mec3 Domain Proteins as Mechanotransducers in Endothelial and Vascular Smooth Muscle Cells

Arterial hypertension is the leading risk factor for cardiovascular morbidity and mortality worldwide. However, little is known about the cellular mechanisms underlying it. In small arteries and arterioles, a chronic increase in blood pressure raises wall tension and hence stretches, namely, the medial vascular smooth muscle cells (VSMC) but also endothelial cell (EC) to cell contacts. Initially compensated by an increase in vascular tone, the continuous biomechanical strain causes a prominent change in gene expression in both cell types, frequently driving an arterial inward remodeling process that ultimately results in a reduction in lumen diameter, stiffening of the vessel wall, and fixation of blood pressure, namely, diastolic blood pressure, at the elevated level. Sensing and propagation of this supraphysiological stretch into the nucleus of VSMC and EC therefore seems to be a crucial step in the initiation and advancement of hypertension-induced arterial remodeling. Focal adhesions (FA) represent an important interface between the extracellular matrix and Lin11-Isl1-Mec3 (LIM) domain-containing proteins, which can translocate from the FA into the nucleus where they affect gene expression. The varying biomechanical cues to which vascular cells are exposed can thus be rapidly and specifically propagated to the nucleus. Zyxin was the first protein described with such mechanotransducing properties. It comprises 3 C-terminal LIM domains, a leucine-rich nuclear export signal, and N-terminal features that support its association with the actin cytoskeleton. In the cytoplasm, zyxin promotes actin assembly and organization as well as cell motility. In EC, zyxin acts as a transcription factor, whereas in VSMC, it has a less direct effect on mechanosensitive gene expression. In terms of homology and structural features, lipoma preferred partner is the nearest relative of zyxin among the LIM domain proteins. It is almost exclusively expressed by smooth muscle cells in the adult, resides like zyxin at FA but seems to affect mechanosensitive gene expression indirectly, possibly via altering cortical actin dynamics. Here, we highlight what is currently known about the role of these LIM domain proteins in mechanosensing and transduction in vascular cells.

Gut Microbiota and Their Derived Metabolites, a Search for Potential Targets to Limit Accumulation of Protein-Bound Uremic Toxins in Chronic Kidney Disease.

Chronic kidney disease (CKD) is characterized by gut dysbiosis with a decrease in short-chain fatty acid (SCFA)-producing bacteria. Levels of protein-bound uremic toxins (PBUTs) and post-translational modifications (PTMs) of albumin increase with CKD, both risk factors for cardiovascular morbidity and mortality. The relationship between fecal metabolites and plasma concentrations of PBUTs in different stages of CKD (n = 103) was explored. Estimated GFR tends to correlate with fecal butyric acid (BA) concentrations (rs = 0.212; p = 0.032), which, in its turn, correlates with the abundance of SCFA-producing bacteria. Specific SCFAs correlate with concentrations of PBUT precursors in feces. Fecal levels of p-cresol correlate with its derived plasma UTs (p-cresyl sulfate: rs = 0.342, p < 0.001; p-cresyl glucuronide: rs = 0.268, p = 0.006), whereas an association was found between fecal and plasma levels of indole acetic acid (rs = 0.306; p = 0.002). Finally, the albumin symmetry factor correlates positively with eGFR (rs = 0.274; p = 0.005). The decreased abundance of SCFA-producing gut bacteria in parallel with the fecal concentration of BA and indole could compromise the intestinal barrier function in CKD. It is currently not known if this contributes to increased plasma levels of PBUTs, potentially playing a role in the PTMs of albumin. Further evaluation of SCFA-producing bacteria and SCFAs as potential targets to restore both gut dysbiosis and uremia is needed.

Risk of chronic kidney disease in patients with obstructive sleep apnea.

Chronic kidney disease (CKD) is a global health concern and a major risk factor for cardiovascular morbidity and mortality. Obstructive sleep apnea (OSA) may exacerbate this risk by contributing to the development of CKD. This study investigated the prevalence and patient awareness of the risk of CKD progression in individuals with OSA. Adults referred to five Canadian academic sleep centers for suspected OSA completed a questionnaire, a home sleep apnea test or in-lab polysomnography and provided blood and urine samples for measurement of estimated glomerular filtration rate (eGFR) and the albumin:creatinine ratio (ACR), respectively. The risk of CKD progression was estimated from a heat map incorporating both eGFR and ACR. 1295 adults (42% female, 54 ± 13 years) were categorized based on the oxygen desaturation index (4% desaturation): <15 (no/mild OSA, n = 552), 15-30 (moderate OSA, n = 322), and >30 (severe OSA, n = 421). After stratification, 13.6% of the no/mild OSA group, 28.9% of the moderate OSA group, and 30.9% of the severe OSA group had a moderate-to-very high risk of CKD progression (p < .001), which was defined as an eGFR <60 mL/min/1.73 m2, an ACR ≥3 mg/mmol, or both. Compared to those with no/mild OSA, the odds ratio for moderate-to-very high risk of CKD progression was 2.63 (95% CI: 1.79-3.85) for moderate OSA and 2.96 (2.04-4.30) for severe OSA after adjustment for CKD risk factors. Among patients at increased risk of CKD progression, 73% were unaware they had abnormal kidney function. Patients with moderate and severe OSA have an increased risk of CKD progression independent of other CKD risk factors; most patients are unaware of this increased risk.

Statin-Associated Myopathy: Emphasis on Mechanisms and Targeted Therapy.

Hyperlipidemia is a major risk factor for cardiovascular morbidity and mortality. Statins are the first-choice therapy for dyslipidemias and are considered the cornerstone of atherosclerotic cardiovascular disease (ASCVD) in both primary and secondary prevention. Despite the statin-therapy-mediated positive effects on cardiovascular events, patient compliance is often poor. Statin-associated muscle symptoms (SAMS) are the most common side effect associated with treatment discontinuation. SAMS, which range from mild-to-moderate muscle pain, weakness, or fatigue to potentially life-threatening rhabdomyolysis, are reported by 10% to 25% of patients receiving statin therapy. There are many risk factors associated with patient features and hypolipidemic agents that seem to increase the risk of developing SAMS. Due to the lack of a “gold standard”, the diagnostic test for SAMS is based on a clinical criteria score, which is independent of creatine kinase (CK) elevation. Mechanisms that underlie the pathogenesis of SAMS remain almost unclear, though a high number of risk factors may increase the probability of myotoxicity induced by statin therapy. Some of these, related to pharmacokinetic properties of statins and to concomitant therapies or patient characteristics, may affect statin bioavailability and increase vulnerability to high-dose statins.

Correlations between sympathetic nervous system activity and smoking, as well as unattended blood pressure in essential hypertension

Abstract Background/Introduction It is a well-known fact that the sympathetic nervous system is involved with the pathophysiology of hypertension. Smoking, which is one of the most significant risk factors for cardiovascular morbidity and mortality, also contributes to the development of hypertension mainly through the stimulation of the sympathetic nervous system. Moreover, measurement of unattended blood pressure (BP) may provide additional information compared to conventionally attended BP. Purpose The aim of this study was to demonstrate the impact of smoking on sympathetic nervous system stimulation, and on BP measurement variations with and without medical supervision. Methods We studied patients with essential hypertension, who were separated into two groups, depending on their smoking habits (Group I: non-smokers, Group II: smokers). In all participants, sympathetic drive was assessed by MSNA estimations based on established methodology (microneurography). Both unattended (patient alone in the room, an oscillometric device programmed to perform 3 BP measurements, at 1-minute intervals, after 5 minutes of rest) and attended BP measurements were conducted with the same device, on the same day of MSNA recording, in random order. Then, we compared the two BP measurement values of each patient to assess which of the two was higher. Results Ninety-two consecutive patients (58±11 years, 50 males) were evaluated. Smokers (n=19) did not differ as regards 24-h ambulatory BP levels, glucose levels, renal function and left ventricular mass index when compared to non-smokers (n=73). However, higher levels of MSNA were recorded to smokers (73.16±13.42 vs. 61.04±18.10 bursts per 100 heartbeats, p&amp;lt;0.01). Furthermore, higher percentage of smokers recorded to have unattended BP values higher than attended (73.7% vs. 47.9% of them respectively, p=0.045). In particular, in smokers unattended BP was higher than attended by 10.07±6.7 mmHg, while in non-smokers unattended BP was lower than attended by 6.6±7.14 mmHg. No correlation was found between the MSNA and the differences observed in the two values resulting from the two different measurements of BP, maybe due to the small size of the sample. Conclusions Cigarette smoking is accompanied with higher sympathetic nervous system activation. Moreover, smokers exhibit higher unattended blood pressure values than normal measurements. The emerging hypothesis is that the stimulation of the sympathetic system causes this difference in measurements. A larger sample of patients is needed to fully determine the clinical significance of the above observation. Funding Acknowledgement Type of funding sources: None.

Prevalence of Left Ventricular Diastolic Dysfunction by Tissue Doppler Imaging in Patients with End Stage Renal Disease undergoing Regular Dialysis with Preserved Systolic Function

Abstract Background Left ventricular hypertrophy (LVH) is the principal myocardial alteration in patients with ESRD due to multiple preload and afterload factors related to hemodialysis leading to left ventricular diastolic dysfunction manifested by signs and symptoms of heart failure with preserved ejection fraction (HFpEF). The use of echocardiography and tissue Doppler imaging is essential to detect diastolic dysfunction in ESRD patients undergoing hemodialysis as the prevalence of diagnosing HFpEF in ESRD patients is under-estimated. Objective To evaluate the possible impact of renal replacement therapy in the form of regular dialysis provided to end stage renal disease patients on left ventricular diastolic function by implementing tissue doppler imaging. Patients and Methods The study included 100 ESRD patients on regular dialysis presenting to the dialysis unit in Ain Shams University Hospitals. The inclusion criterion was end stage renal disease patients with GFR &amp;lt; 15 ml/min/1.73 m2 on regular dialysis for more than 6 months. Excluded patients were those above than 80 yrs old, with hemodynamic instability, arrhythmias, valvular diseases, ischemic conditions, and LV systolic dysfunction. After the hemodialysis session, ECG gated echocardiography was done applying pulsed wave Doppler on mitral valve to detect E/A ratio, continuous wave Doppler on tricuspid valve to calculate TR vmax, and tissue Doppler on lateral mitral annulus to detect e’ and E/e’ ratio. Moreover, left atrial volume index (LAVI) and other standard echocardiographic parameters were measured. Full history and clinical examination including ECG recording was done and blood samples were taken to measure hemoglobin levels. Patients were then stratified according to their diastolic dysfunction grading. Results Seventy eight percent (78%) of the patients showed diastolic dysfunction including 46 % showed grade I diastolic dysfunction, 26 % showed grade II diastolic dysfunction and 6% showed grade III diastolic dysfunction. Hemoglobin levels showed significant negative correlation with E, E/A, E/E’, LAVI and TR Vmax (r = -0.25, -0.37, -0.29, -0.23 and -0.31 with p 0.012, &amp;lt;0 .001, &amp;lt; 0.003, 0.002 &amp; &amp;lt;0 .001 respectively). Multiple regression analysis revealed smoking, DM, Hb, LVPWd, EF, E/A, LAVI and TR Vmax presented the important determinants of diastolic filling (β = -0.16, 0.15, -0.20, -0.27, -0.25, 0.16, 0.39 &amp; 0.27 and p = 0.002, 0.045, &amp;lt; 0.001, 0.022, &amp;lt; 0.001, 0.039, &amp;lt; 0.001 &amp; &amp;lt; 0.001 respectively). Comparing E/A ratio with E/e’ ratio sensitivities revealed E/A ratio was 28.2% while E/e’ ratio was 74.3%. This was statistically significant showing a difference between the two modalities (χ2 = 33.2526 and p = &amp;lt; 0 .0001). Conclusion In ESRD patients, maladaptive events leading to LVH and diastolic dysfunction occur frequently. Thus, early identification and treatment of factors involved in order to prevent this devastating process. Now it seems that TDI and E, E/A and E/E’ parameters are good instruments for the early detection of LVH and diastolic dysfunction as they are important risk factors for cardiovascular morbidity and mortality in CKD. In comparison with the conventional Doppler techniques, tissue Doppler is a vital tool in diagnosing diastolic dysfunction.

Hepatic and Vascular Vitamin K Status in Patients with High Cardiovascular Risk

Vitamin K dependent proteins (VKDP), such as hepatic coagulation factors and vascular matrix Gla protein (MGP), play key roles in maintaining physiological functions. Vitamin K deficiency results in inactive VKDP and is strongly linked to vascular calcification (VC), one of the major risk factors for cardiovascular morbidity and mortality. In this study we investigated how two vitamin K surrogate markers, dephosphorylated-undercarboxylated MGP (dp-ucMGP) and protein induced by vitamin K absence II (PIVKA-II), reflect vitamin K status in patients on hemodialysis or with calcific uremic arteriolopathy (CUA) and patients with atrial fibrillation or aortic valve stenosis. Through inter- and intra-cohort comparisons, we assessed the influence of vitamin K antagonist (VKA) use, vitamin K supplementation and disease etiology on vitamin K status, as well as the correlation between both markers. Overall, VKA therapy was associated with 8.5-fold higher PIVKA-II (0.25 to 2.03 AU/mL) and 3-fold higher dp-ucMGP (843 to 2642 pM) levels. In the absence of VKA use, non-renal patients with established VC have dp-ucMGP levels similar to controls (460 vs. 380 pM), while in HD and CUA patients, levels were strongly elevated (977 pM). Vitamin K supplementation significantly reduced dp-ucMGP levels within 12 months (440 to 221 pM). Overall, PIVKA-II and dp-ucMGP showed only weak correlation (r2 ≤ 0.26) and distinct distribution pattern in renal and non-renal patients. In conclusion, VKA use exacerbated vitamin K deficiency across all etiologies, while vitamin K supplementation resulted in a vascular VKDP status better than that of the general population. Weak correlation of vitamin K biomarkers calls for thoughtful selection lead by the research question. Vitamin K status in non-renal deficient patients was not anomalous and may question the role of vitamin K deficiency in the pathogenesis of VC in these patients.

Secondhand Smoke Decreased Excitability and Altered Action Potential Characteristics of Cardiac Vagal Neurons in Mice.

Background: Secondhand smoke (SHS), a major indoor pollutant, is a significant risk factor for cardiovascular morbidity and mortality including arrhythmias and sudden cardiac death. Exposure to SHS can produce autonomic imbalance, as evidenced by reduced heart rate variability (HRV)—a clinical metric of cardiac vagal regulation. Currently, the mechanisms through which SHS changes the vagal preganglionic neuronal inputs to the heart to produce this remains unknown.Objectives: To characterize the effect of SHS on both the excitability and action potential (AP) characteristics of anatomically identified cardiac vagal neurons (CVNs) in the nucleus ambiguus and examine whether SHS alters small conductance calcium-activated potassium (SK) channel activity of these CVNs.Methods: Adult male mice were exposed to four weeks of filtered air or SHS (3 mg/m3) 6 h/day, 5 day/week. Using patch-clamp recordings on identified CVNs in brainstem slices, we determined neuronal excitability and AP characteristics with depolarizing step- and ramp-current injections.Results: Four weeks of SHS exposure reduced spiking responses to depolarizing current injections and increased AP voltage threshold in CVNs. Perfusion with apamin (20 nM) magnified these SHS-induced effects, suggesting reduced SK channel activity may serve to minimize the SHS-induced decreases in CVNs excitability. Medium afterhyperpolarization (a measurement of SK channel activity) was smaller in the SHS group, further supporting a lower SK channel activity. AP amplitude, rise rate, fast afterhyperpolarization amplitude (a measurement of voltage-gated channel activity), and decay rate were higher in the SHS group at membrane voltages more positive to 0 mV, suggesting altered inactivation properties of voltage-dependent channels underlying APs.Discussion: SHS exposure reduced neuronal excitability of CVNs with compensatory attenuation of SK channel activity and altered AP characteristics. Neuroplasticity of CVNs could blunt regulatory cardiac vagal signaling and contribute to the cardiovascular consequences associated with SHS exposure, including reduced HRV.

Relation between carotid intimal medial thickness and left ventricular mass and left ventricular mass indices in maintenance hemodialysis patients.

Left ventricular hypertrophy (LVH) is a risk factor of cardiovascular morbidity in dialysis patients. The association between LV mass and carotid intimal medial thickness (CIMT) could be due to increased hemodynamic load in dialysis patients. The relationship between CIMT and LVM indices in hemodialysis (HD) patients was investigated. This is a cross-sectional study including 65 HD patients, divided into two groups: Group 1 with CIMT ≤ 1 mm (N=29), Group 2 with CIMT > 1 mm (N=36). Echocardiographic evaluation of the LVM, CIMT measurement using B-mode ultrasonography, patients' basic clinical and biochemical data were recorded. Patients with CIMT > 1 mm (Group 2) showed significantly higher LVM, LVM/BSA (body surface area), and LVM/Ht2.7 (height). Regarding linear regression, CIMT was found to be an independent predictor for LVM, LVM/BSA, and LVM/Ht2.7 . LVM, LVMI, and LVM/Ht2.7 are significantly elevated in HD patients with CIMT > 1 mm group. CIMT was found to be the independent predictor for LVH in maintenance HD patients.

Arterial hypertension and antihypertensive therapy in older patients. The agreed opinion of experts from the Russian Association of Gerontologists and Geriatricians, the Antihypertensive League, the National Society for Preventive Cardiology

High blood pressure is a risk factor for cardiovascular morbidity and mortality, as well as cognitive decline and loss of autonomy in the elderly and old age. Randomized clinical trials (RCTs) in populations of older patients living at home with low comorbidity and preserved autonomy indicate the benefit of lowering elevated blood pressure in patients over 80 years of age. Older patients with senile asthenia, loss of autonomy and other geriatric problems were excluded from RCTs, and observational studies in these groups of patients indicate an increase in morbidity and mortality with lower blood pressure and antihypertensive therapy. Obviously, in very elderly patients, a universal strategy for the treatment of arterial hypertension cannot be applied due to the significant heterogeneity of their functional status. The geriatric approach to the management of arterial hypertension in older patients involves an assessment of the functional status, the presence of senile asthenia, and the degree of autonomy for the choice of antihypertensive therapy tactics.

The effect of hidden female smoking on the relationship between smoking and cardiovascular disease.

Smoking is a known risk factor for cardiovascular morbidity and mortality, but several Korean studies have shown differing results on the association of current smoking status and the risk of cardiovascular disease (CVD). The aim of the present study was to investigate the association between smoking status and CVD (myocardial infarction and stroke) using national representative populationbased samples. The aim was also to investigate the effects of hidden smokers on the association between CVD and smoking. Data were acquired from 28,620 participants (12,875 men and 15,745 women), age 19 years or older, who participated in the Korea National Health and Nutrition Examination Survey (KNHANES) conducted from 2008 to 2016. The multivariable logistic regression analysis showed that ex-smoking status was correlated with CVD when self-reported (odds ratio [OR]: 1.62; 95% confidence interval [CI]: 1.20-2.19) and for survey-cotinine verified-smoking status (OR: 1.57; 95% CI: 1.20-2.19). Interestingly, the present study showed current smoking was not significantly associated with CVD. For the effect of sex on smoking and CVD, self-reported and survey-cotinine-verified ex-smoking status were correlated with CVD in males (OR: 1.45; 95% CI: 1.04-2.04 and OR: 1.43; 95% CI: 1.02-2.02) and in females (OR: 2.74; 95% CI: 1.59-4.71 and OR: 2.92; 95% CI: 1.64-5.18). The ratios of cotinine-verified to self-reported smoking rates were 1.95 for women and 1.08 for men. In the current study, while ex-smoking status was significantly associated with CVD, current smoking status was not. Female ex-smoking status had a higher adjusted odds ratio for CVD than males compared to non-smoking status. An effect of hidden female smoking was also found on the association between smoking status and CVD in Korean adults.

Abstract P156: Intimal And Medial Calcification Underlie Differential Molecular Mechanisms

Introduction: Vascular calcification (VC) is a significant risk factor for cardiovascular morbidity and mortality. Based on the mineral deposition site in the arterial wall, VC classifies into intimal and medial calcification. We hypothesize that distinct in vitro mineralization methods promote specific intracellular signalling pathways in vascular smooth muscle cells (SMC), reflecting both VC types. Methods and Results: Human coronary artery SMCs were cultured in osteogenic medium (OM) or high calcium-phosphate medium (CaP) to induce calcification. OM resembles SMCs differentiation in intimal calcification - a key process in atherosclerotic plaque remodeling. CaP is associated with chronic kidney disease - a risk factor for medial calcification. Transcriptomics revealed a distinct gene expression profile of OM and CaP-calcifying SMCs, that share 6.9% and 11.3% of their genes, respectively. The 109 shared dysregulated genes between OM and CaP-calcifying SMCs highlighted enriched pathways related to SMC contraction and metabolism. Real-time extracellular efflux analysis demonstrated a different metabolic profile in OM and CaP-calcifying SMCs. We observed decreased mitochondrial respiration and glycolysis (-57,3% p=0.029) by CaP and increased mitochondrial respiration without altered glycolysis by OM. Subsequent kinome and in silico drug repurposing analysis (Connectivity Map) revealed a distinct role of protein kinase C (PKC). Validation using prostratin, a specific PKC activator, demonstrated differential effects on matrix mineralization that was decreased by OM (-69,3%, p&lt;0.001) and increased by CaP (+69,6%, p=0.044). Conclusions: In conclusion, OM and CaP-induced SMC calcification underlies differential mechanisms in vitro. Therefore, research should distinguish between the two aspects of VC and increased knowledge about the underlying pathophysiological mechanisms may open the possibility for preventing intimal and medial calcification.