Risk Factor For Cardiovascular Morbidity Research Articles

Sağlıklı Erişkinlerde İstirahat Kalp Hızı Oksidatif Stresle İlişkili Değildir

Introduction: Although resting heart rate (RHR) and oxidative stress are risk factors for cardiovascular morbidity and mortality, the association between them has not been fully understood. The aim of the present study was to investigate the relationship between RHR and oxidative/antioxidative stress markers. Patients and Methods: The study consisted of 56 healthy volunteers (33 males; mean age: 44.1 ± 9.0 years). Subjects were divided into two groups according to heart rate quartiles: lower two quartiles as group 1 (n= 29) and upper two quartiles as group 2 (n= 27). We measured total oxidant status (TOS), total antioxidant capacity (TAC), oxidative stress index (OSI), and ceruloplasmin (CP) levels of subjects. Results: There was no any significant difference in baseline clinical characteristics and laboratory measurements between the groups (p> 0.05 for all variables). Mean RHRs were 71.3 ± 4.6 in group 1 and 82.4 ± 4.1 in group 2. The TAC, TOS, OSI, and CP levels were similar between the two groups (p> 0.05 for all variables). We did not detect any significant association between RHR and oxidative/antioxidative parameters. Conclusion: RHR was not associated with TOS, TAC, OSI, and CP levels in our study.

Improved scoring system for the electrocardiographic diagnosis of left ventricular hypertrophy.

BACKGROUNDLeft ventricular hypertrophy (LVH) is a common manifestation of cardiovascular disease and a risk factor for cardiovascular morbidity and mortality, but available methods for its electrocardiographic (ECG) diagnosis have limited accuracy.AIMTo investigate findings associated with LVH on ECG and developed an improved system for the diagnosis of LVH.METHODSA cohort study comparing ECG data acquired within 30 days of transthoracic echocardiography (TTE) was performed. Multivariate regression analysis identified ECG findings associated with increased LV mass and mass index. A scoring system was derived and performance compared to established criteria for LVH.RESULTSData from 5486 outpatients with TTEs and corresponding ECGs were included in the derivation cohort, 333 (6.1%) of whom had LVH by TTE. In the primary regression analysis, findings associated with LVH were amplitudes of Q in V3, R in V6, S in V3, T in V6, P’ in V1, P in V6, as well as R and T-axis discordance, R peak time in V6, QRS duration, weight, height, sex, and age. From this we derived a score consisting of 5 criteria, and validated it in an independent cohort of 910 patients. With a threshold of 1.5 points, sensitivity and specificity were 67.9% and 81.4%, and 62.5% and 83.2% in the derivation and validation cohorts, respectively. With a threshold of 2 points, sensitivity and specificity were 42.3% and 93.0%, and 37.5% and 93.4% in these cohorts.CONCLUSIONSThis score had superior sensitivity for detection of LVH by ECG while making a modest sacrifice in specificity compared to conventional criteria.

KDOQI US Commentary on the 2017 ACC/AHA Hypertension Guideline

Hypertension is a modifiable risk factor for cardiovascular morbidity and mortality and reduction of elevated blood pressure (BP) remains an important intervention for slowing kidney disease progression. Over the past decade, the most appropriate BP target for initiation and titration of BP-lowering medications has been an area of intense research and debate within the clinical community. In 2017, the American College of Cardiology and the American Heart Association (ACC/AHA) in conjunction with several other professional societies released new hypertension guidelines based on data from a systematic review of clinical trials and observational data. While many of the recommendations in the ACC/AHA hypertension guideline are relevant to nephrology practice, BP targets and management strategies for patients receiving dialysis are not discussed. This Kidney Disease Outcomes Quality Initiative (KDOQI) commentary focuses largely on recommendations from the ACC/AHA hypertension guidelines that are pertinent to individuals at risk of chronic kidney disease or with non-dialysis-dependent chronic kidney disease. This KDOQI commentary also includes a brief discussion of the consensus statement regarding hypertension diagnosis and management for adults receiving maintenance dialysis published by the European Renal and Cardiovascular Medicine Working Group of the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) and the Hypertension and the Kidney working group of the European Society of Hypertension. Overall, we support the vast majority of the ACC/AHA recommendations and highlight select areas in which best diagnosis and treatment options remain controversial.

Neuroimmune crosstalk in the pathophysiology of hypertension.

Hypertension is an important risk factor for cardiovascular morbidity and mortality andfor events such as myocardial infarction, stroke, heart failure and chronic kidney disease and is a major determinant of disability-adjusted life-years. Despite the importance of hypertension, the pathogenesis of essential hypertension, which involves the complex interaction of several mechanisms, is still poorly understood. Evidence suggests that interplay between bone marrow, microglia and immune mediators underlies the development of arterial hypertension, in particular through mechanisms involving cytokines and peptides, such as neuropeptide Y, substance P, angiotensin II and angiotensin-(1-7). Chronic psychological stress also seems to have a role in increasing the risk of hypertension, probably through the activation of neuroimmune pathways. In this Review, we summarize the available data on the possible role of neuroimmune crosstalk in the origin and maintenance of arterial hypertension and discuss the implications of this crosstalk for recovery and rehabilitation after cardiac and cerebral injuries.

Abstract P286: Short-Term Repeatability of Electrocardiographic Criteria of Left Ventricular Hypertrophy

Background: Left ventricular hypertrophy (LVH) is a marker of cardiac end-organ damage and a risk factor for cardiovascular morbidity and mortality. Although electrocardiogram (ECG) is the most common tool for LVH assessment in contemporary clinical trials and cohort studies, the repeatability of ECG-LVH criteria has not been sufficiently examined. Objectives: Characterize the repeatability and minimal detectable change of ECG-LVH criteria. Methods: A total of 63 participants (mean age 50 years; 31 females) underwent two visits one week apart. At each visit, two digital ECGs were obtained following a standardized protocol. The ECG data were processed centrally to automatically obtain waveform measurements needed to calculate Cornell voltage (CV) LVH (SV3 + RaVL >2800 μV for men and >2000 μV for women), Cornell voltage product (CVP) LVH ((RaVL + SV3) X QRS duration ≥244 mV sec; for both Cornell criteria, 0.8 mV was added to the voltage sum for women), and Sokolow-Lyon (SL) LVH (SV1 +RV5/V6 ≥3500 μV). In addition to using these criteria as dichotomous LVH variables, we also used the waveforms measurements composing them as continuous variables, referred to here as CV-index, CVP-index, and SL-index. We used random-effects, mixed models to parse the variance of the variables into their between-participant, between-visit, and within-visit components, and calculated the intra-class correlation coefficient (ICC), minimal detectable change (95% confidence), and Kappas. Results: Between-participant variation accounted for 93% to 97% of the total variation in CV-index, CVP-index, and log of SL-index. The ICCs (95% confidence intervals) were 0.97 (0.96, 0.98) for CV-index, 0.97 (0.95, 0.98) for CVP-index, and 0.93 (0.90, 0.96) for log of SL-index. Minimal detectable change between repeat measures of CV-index, CVP-index, and log of SL-index were ≥236.7 μV, ≥26.7 mV, and ≥0.09 μV, respectively. The within-visit Kappa (95% confidence limits) was 0.73 (0.38, 1.00) for SL LVH and 1 for the other two LVH criteria. The between-visit Kappa was 1 for CV LVH, 0.66 (0.04, 1.00) for CVP LVH, and 0.40 (-0.03, 0.83) and 0.64 (0.26, 1.00) for the SL LVH first and second measurements of each visit, respectively. When defining ECG-LVH as presence of ≥1 ECG-LVH criteria, the within visit Kappa became 0.78 (0.49, 1.00) for the first visit and 1 for the second visit; the between visit Kappa values became 0.50 (0.12, 0.88) and 0.70 (0.38, 1.00) for the first and second measurements of each visit. Conclusion: CV, CVP, SL indices as continuous variables have excellent repeatability. The dichotomous ECG-LVH criteria have excellent within visit agreement, but between visit agreement ranges from fair to poor, which improved by combining multiple criteria. These results alleviate concerns about the repeatability the ECG LVH use in clinical trials and epidemiologic studies.

Relationship between arterial stiffness and circadian pattern of blood pressure.

Arterial stiffness is a risk factor for cardiovascular morbidity and mortality. The relationship between the arterial stiffness and the circadian pattern of blood pressure (BP) has been controversial. The objective of the present study was to investigate the relationship between arterial stiffness by pulse wave analysis (PWA) and variables of 24-hour ambulatory BP monitoring (ABPM) in patients with high normal BP or hypertension (HTN).Five hundred forty-eight patients (304 males, 48 ± 12-year-old) with high normal BP or HTN were enrolled. BP was measured at the outpatient clinic and 24-hour ABPM was performed. Using radial applanation tonometry, PWA was performed for evaluation of systemic arterial stiffness. Patients were classified into four groups according to the dipping patterns: a nocturnal dipping group, an isolated systolic non-dipping group, an isolated diastolic non-dipping group and a both systolic and diastolic non-dipping group. For adjustment of age, population was divided to 2 groups: old group ≥55 year-old (n = 158, 75 males), young group <55 year-old (n = 390, 229 males).According to the dipping patterns, augmentation pressure (AP), augmentation index (AI) and heart rate (75 bpm) adjusted AI (AI@HR75) showed statistically significant difference (P = .011, .009, and .018, respectively). Multivariate analysis showed that isolated diastolic non-dipping was correlated with arterial stiffness expressed as AI and AI@HR 75, only in young group (β-coefficient = 12.6, P = .04 and β-coefficient = 7.503, P = .028, respectively).Arterial stiffness might be closely related with the pattern of non-dipping in young patients with HTN and high normal BP.

Association of Adolescent Hypertension With Future End-stage Renal Disease

Hypertension is a leading risk factor of cardiovascular morbidity and mortality. The role of nonmalignant hypertension as the sole initiating factor of end-stage renal disease (ESRD) in non-African American populations has recently been questioned. To investigate the association between hypertension and future ESRD in otherwise healthy adolescents. This retrospective cohort study examined the data of 16- to 19-year-old healthy candidates for military service in the Israel Defense Forces between January 1, 1967, and December 31, 2013. Data were obtained from the central conscription registry of the Israel Defense Forces and the ESRD registry of the Israel Ministry of Health. Participants underwent a comprehensive medical assessment prior to their military service. Individuals with evidence of renal damage or kidney-related risk factors were excluded. The data analysis was conducted from February 12, 2017, to October 16, 2018. End-stage renal disease as recorded by the Israeli ESRD registry, including hemodialysis, peritoneal dialysis, renal transplant diagnosed between January 1, 1990, and December 31, 2014. The cohort included 2 658 238 adolescents (1 596 709 [60.1%] male with a mean [SD] age of 17.4 [0.5] years), of whom 7997 (0.3%) had an established hypertension diagnosis. Half of the individuals in the hypertensive group were overweight (1559 [20.1%]) or obese (2243 [28.9%]), and most (7235 [90.5%]) were male. During a median follow-up of 19.6 years (52 287 945 person-years), 2189 individuals developed ESRD, with an incidence rate of 3.9 per 100 000 person-years. Adolescent hypertension was found to be associated with future ESRD (crude hazard ratio [HR], 5.07; 95% CI, 3.73-6.88). In a multivariable model adjusted for sex, age, years of education, body mass index, and other sociodemographic variables, the HR was 1.98 (95% CI, 1.42-2.77). When excluding participants with severe hypertension, the association with ESRD remained statistically significant (HR, 1.93; 95% CI, 1.37-2.70). In the subanalysis of nonoverweight adolescents, the association between hypertension and ESRD was statistically significant as well (HR, 2.11; 95% CI, 1.05-4.24). Hypertension appears to be associated with a doubling of the risk of future ESRD in an otherwise healthy adolescent population.

Characteristics of visit-to-visit blood pressure variability in hemodialysis patients.

Visit-to-visit blood pressure variability (VVBPV) is an independent risk factor for cardiovascular morbidity and mortality in the general population. Hemodialysis (HD) patients have a poor prognosis due to an increased prevalence of cardiovascular disease. Intradialytic hypotension is associated with excess mortality, but whether VVBPV influences mortality is still unclear in HD patients. The present study aimed to investigate the characteristics of VVBPV in these patients. A total of 324 maintenance HD patients, who could be followed for 60 months, were recruited. We used variation independent of the mean (VIM) in pre-dialysis systolic blood pressure (pre-VIM-SBP) as an index of VVBPV. We investigated (1) the reproducibility of pre-VIM-SBP, (2) the relationship between pre-VIM-SBP and background factors, and (3) the association between pre-VIM-SBP and mortality. Pre-VIM-SBP showed significant reproducibility [intraclass correlation, 0.45 (P < 0.001)]. Higher pre-VIM-SBP was associated with less physical activity and worse left ventricular diastolic function. Higher pre-VIM-SBP was associated with a higher rate of cardiovascular deaths independent of other factors. These data suggest that VVBPV in HD patients is reproducible and associated with various background factors. VVBPV is independently correlated with cardiovascular mortality (hazard ratio: 1.166, 95% confidence interval: 1.030-1.320, P = 0.015). Further studies are necessary to confirm the mechanism of increased VVBPV and to clarify whether reducing VVBPV will improve the prognosis for HD patients.

Peculiarities of cardiovascular remodeling in hypertensive patients at high additional risk with concomitant subclinical hypothyroidism

Arterial hypertension affects over 12 million people in Ukraine, which accounts for about 30 % of the adult population, and is a powerful independent risk factor for cardiovascular morbidity and mortality. Subclinical hypothyroidism (SH) is also an independent causative factor of the cardiovascular risk and is associated with the development of ischemic heart disease, myocardial infarction, chronic heart failure and increased mortality from cardiovascular diseases regardless of sex, age or pre-existing cardiac pathology. Therefore, there is a need to study the influence of subclinical hypothyroidism on the cardiovascular remodeling peculiarities in patients with arterial hypertension (AH). Material and methods. The study involved 124 patients with AH stage II divided into two groups. The group of patients with AH without SH included 92 patients (women 81.52 % (75), men 18.48 % (17)) and 32 patients (women 87.5 % (28), men 12.5 % (4)) represented the group with AH and concomitant SH. The groups of patients were comparable in age (P = 0.093), sex (P = 0.44319), height (P = 0.993), weight (P = 0.719), body surface area (P = 0.901), body mass index (P = 0.669). In all patients underwent arterial blood pressure measurement (OMRON 750 IT,Japan), echocardiography and ultrasound of carotid arteries using the original QIMT software on My Lab 50 (Esaote,Italy). Results. In patients with AH with the concomitant SH, in contrast to patients with AH without SH, a significant increase in indexes of the intima-media complex thickness of the right common carotid artery by 8.2% (P < 0.05) and the left common carotid artery by 7.9 % (P < 0.05) was observed. Changes of structural, geometrical and functional indexes of the heart in patients with AH and SH were significant increase in the left atrial size by 3.5 % (P < 0.05), end diastolic size by 3.0 % (P < 0.05) and end systolic size of the left ventricle by 2.3 % (P < 0.05), myocardial mass index by 11.1 % (P < 0.05), index Е/Е´ by 13.0 % (P < 0.05), gradient of transpulmonary flow by 6.6 % (P < 0.05) in comparison to patients with AH without SH. Conclusions. In patients with AH and concomitant SH in contrast to patients with AH without SH, an increase in thickness of the intima-media complex of both common carotid arteries with comparable diameters of vessels has been established, as well as increase in size of the left atrium, left ventricular myocardial mass index mainly due to the left ventricular dilation, Е/Е´ index and pressure gradient in the pulmonary artery suggesting an increase in the end diastolic pressure and the left ventricular diastolic dysfunction.

Low-Grade Albuminuria Is Associated with Left Ventricular Hypertrophy and Diastolic Dysfunction in Patients with Hypertension

Introduction: Microalbuminuria is a risk factor for cardiovascular morbidity and mortality in hypertensive patients. However, the relationship between low-grade albuminuria, a higher level of albuminuria below microalbuminuria threshold, and hypertension-related organ damage is unclear. Left ventricular (LV) hypertrophy (LVH) is well recognized to be a subclinical organ damage of hypertension, and LV diastolic dysfunction is also reported to be an early functional cardiac change of hypertension that predicts heart failure. The present study aimed to investigate the association of low-grade albuminuria with LVH and LV diastolic dysfunction in hypertensive patients. Methods: This cross-sectional observational clinical study was retrospectively performed in 870 hypertensive patients admitted to our hospital. Urinary albumin to creatinine ratio (UACR) was calculated to assess the levels of albuminuria: macroalbuminuria (≥300 mg/g), microalbuminuria (≥30 mg/g, but <300 mg/g), and normal albuminuria (<30 mg/g). Low-grade albuminuria was defined as sex-specific highest tertile within normal albuminuria (8.1–29.6 mg/g in males and 11.8–28.9 mg/g in females). LVH and LV diastolic dysfunction were identified as recommended by American Society of Echocardiography. Results: Of the 870 patients, 765 (87.9%) had normal albuminuria, 77 (8.9%) had microalbuminuria, and 28 (3.2%) had macroalbuminuria. Percentage of LVH and LV diastolic dysfunction was increased with ascending UACR. UACR was independently associated with LVH and LV diastolic dysfunction, even in patients with normal albuminuria. Multivariable logistic regression showed that the patients with the highest tertile within normal albuminuria had nearly 80% increase in LVH and nearly 60% increase in LV diastolic dysfunction (adjusted OR for LVH 1.788, 95% CI 1.181–2.708, p = 0.006; adjusted OR for LV diastolic dysfunction 1.567, 95% CI 1.036–2.397, p = 0.034). After further stratification analyses in patients with normal albuminuria, it was shown that this independent association persisted in female patients, those who were younger than 70 years old, and those with duration of hypertension <15 years. Conclusion: Low-grade albuminuria was associated with LVH and LV diastolic dysfunction in hypertensive patients, especially in patients younger than 70 years old, and those with duration of hypertension <15 years.

Electrocardiography versus Echocardiography for assessment of left ventricular hypertrophy in ischemic heart disease patients with and without cardiovascular risk factors

Background: it is well documented that left ventricular hypertrophy (LVH) detected by 12-lead electrocardiography or echocardiography is a major risk factor for cardiovascular morbidity and mortality in cohorts ranging from the general population to those with established cardiovascular disease, including coronary artery disease (CAD). Objectives: aims of this study were to detect prevalence of LVH in CAD patients by standard echocardiography by measuring LVM indexed to body surface area and to test the sensitivity and specificity of new ECG criteria, Peugero-Lo Prosti criteria, for detection of left ventricular hypertrophy and comparing it with other ECG criteria to diagnose LVH. Patients and Methods: This observational cross sectional study was conducted at El-Hussein University Hospital and Minia Health Insurance Hospital during the period from July 2016 to June 2017, the study involved 230 patients of either sex, and referred for Echocardiography department to perform 2D transthoracic echocardiography. Results: In our study, we founded that firstly, the echo-LVH is prevalent in CAD patient (41.5%) regardless the presence of other cardiovascular risk factors. Moreover, our results showed that, the prevalence of echo-LVH is significantly higher in patients with CAD and hypertension, than in patients with CAD only (54% Vs. 32%). Secondly, the Peguero-Lo Prosti criteria has a higher sensitivity (61.4%) for detecting LVH among the patients with CAD than Sokolow-Lyon criteria (26.5%), Cornell voltage criteria (32.5%) and Romhilt Estes point score (41%) considering LVMI by echocardiography as reference standard. Conclusion: the prevalence of echocardiographic LVH in CAD patient is high regardless the presence of other cardiovascular risk factors. Overall the present study shows that, Peguero-Lo Presti criteria has higher sensitivity and specificity in the ECG diagnosis of LVH compared to Sokolow-Lyon criteria, Cornell voltage criteria and Romhilt-Estes point score system considering LV mass index by 2D Echocardiography as reference standard.

Electrocardiography versus Echocardiography for assessment of left ventricular hypertrophy in ischemic heart disease patients with and without cardiovascular risk factors

Background: it is well documented that left ventricular hypertrophy (LVH) detected by 12-lead electrocardiography or echocardiography is a major risk factor for cardiovascular morbidity and mortality in cohorts ranging from the general population to those with established cardiovascular disease, including coronary artery disease (CAD). Objectives: aims of this study were to detect prevalence of LVH in CAD patients by standard echocardiography by measuring LVM indexed to body surface area and to test the sensitivity and specificity of new ECG criteria, Peugero-Lo Prosti criteria, for detection of left ventricular hypertrophy and comparing it with other ECG criteria to diagnose LVH. Patients and Methods: This observational cross sectional study was conducted at El-Hussein University Hospital and Minia Health Insurance Hospital during the period from July 2016 to June 2017, the study involved 230 patients of either sex, and referred for Echocardiography department to perform 2D transthoracic echocardiography. Results: In our study, we founded that firstly, the echo-LVH is prevalent in CAD patient (41.5%) regardless the presence of other cardiovascular risk factors. Moreover, our results showed that, the prevalence of echo-LVH is significantly higher in patients with CAD and hypertension, than in patients with CAD only (54% Vs. 32%). Secondly, the Peguero-Lo Prosti criteria has a higher sensitivity (61.4%) for detecting LVH among the patients with CAD than Sokolow-Lyon criteria (26.5%), Cornell voltage criteria (32.5%) and Romhilt Estes point score (41%) considering LVMI by echocardiography as reference standard. Conclusion: the prevalence of echocardiographic LVH in CAD patient is high regardless the presence of other cardiovascular risk factors. Overall the present study shows that, Peguero-Lo Presti criteria has higher sensitivity and specificity in the ECG diagnosis of LVH compared to Sokolow-Lyon criteria, Cornell voltage criteria and Romhilt-Estes point score system considering LV mass index by 2D Echocardiography as reference standard.

Iznenadna srčana smrt - mere prevencije i preporuke za bavljenje fizičkom aktivnošću

Physical activity provides many well-documented health benefits, while physical inactivity is a leading risk factor for cardiovascular morbidity and mortality. In order to achieve these benefits, one must expose himself to relatively moderate physical activity. However, many athletes and recreationists go beyond these limits and engage in higher level of physical activity. Occasionally, intense physical activity is associated with sudden death in individuals with concealed heart disease. Despite the media attention provided by such accident, the reputation of physical activity remains intact, as most deaths can be explained by a basic cardiac abnormality where exercise is only the trigger of a fatal arrhythmia, not the actual cause of death. The paradox is that athletes with these abnormalities show identical performance in the form of minute heart volume compared to healthy individuals. In athletes younger than 35, congenital heart disease, especially hypertrophic cardiomyopathy and congenital coronary artery abnormalities, are the leading cause of sudden cardiac death, while most athletes older than 35 die due to atherosclerotic changes in the coronary arteries. Pre-competition screening with apparently healthy individuals is the only way to prevent sudden cardiac death in sports. When diagnosing a specific condition of the cardiovascular system, it is necessary to determine the risk of sudden cardiac death associated with continued physical activity and competitive sports activity, and to define clear disqualification criteria for each athlete individually.

A Suggested Clinical Approach for the Diagnosis and Management of ‘Statin Intolerance’

Background: HMG-CoA reductase inhibitors (“statins”) are first-line drugs used for management of hyperlipidaemia, a major risk factor for cardiovascular morbidity and mortality [[1]Wadhera K.R. Steen L.D. Khan I. et al.A review of low-density lipoprotein cholesterol, treatment strategies, and its impact on cardiovascular disease morbidity and mortality, Journal of Clinical Lipidology.. 2016; 10: 472-489Google Scholar]. For each 1.0 mmol/l reduction in low-density lipoprotein cholesterol (LDL-C), statins curb major vascular events by 21% and all-cause mortality by 9% [[2]Cholesterol Treatment Trialists’ (CTT) Collaborators. Efficacy and safety of LDL-lowering therapy among men and women: meta-analysis of individual data from 174,000 participants in 27 randomised trials. Lancet. 2015; 385(9976): 1397-405.Google Scholar]. While statins offer major cardiovascular disease (CVD) risk reduction and a generally excellent safety profile, their widespread use and common misconceptions have resulted in frequent labelling of patients as ‘statin intolerant’, of whom only a subset may be truly intolerant. Methods: We searched databases (PubMed, Embase, CINAHL, Scopus and Cochrane Database of Systematic Reviews) for original and review articles published between 1980 – 2019. Search strategies included MeSH terms and keywords associated with “cardiovascular disease”, “statin intolerance” and “alternative therapies”. Recent guidelines and specialist experience were also sought to conduct a narrative review. Results: Although there is clinical consensus for diagnosing rare side effects such as rhabdomyolysis, confirming that statins cause less common side effects (e.g. memory impairment) has proven difficult. Moreover, there is as yet no strong randomised trial evidence for nearly all these other potential side effects, despite statins being widely investigated globally. A step-wise approach to possible statin intolerance, using consistent definitions and a simple flowchart that we have formulated, will enable better diagnosis and management. Conclusions: Outcomes from this project may potentially enable patients with an established CVD risk to adhere better to statin therapy and subsequently improve cardiovascular outcomes. Potential treatment strategies are emerging including intermittent dosing regimens, emerging drugs and nutraceuticals.

Targeted neurotransmitter metabolomics profiling of oleanolic acid in the treatment of spontaneously hypertensive rats.

Essential hypertension (EH) is a prevalent chronic medical condition and a major risk factor for cardiovascular morbidity and mortality. Neurotransmitters are involved in the physiological process of blood pressure regulation in the body. Studies have shown that oleanolic acid (OA) can effectively regulate neurotransmitter-related metabolic disorders caused by EH, but the mechanism is still unclear. Here, we studied the neurotransmitter metabolic profiles in five brain regions by targeted metabolomics approaches in spontaneously hypertensive rats (SHRs) treated with OA and vehicle. Samples from five brain regions (hippocampus, striatum, hypothalamus, temporal lobe, and frontal lobe) were collected from the control group, the spontaneously hypertensive rat (SHR) group, and the OA group. Targeted metabolomics based on UPLC-Q-Exactive-MS was employed to characterize the dramatically changed neurotransmitters in the brain regions of SHRs treated with OA and vehicle. The expressions of the key enzymes involved in the neurotransmitter metabolism were detected by the reverse transcription-polymerase chain reaction (RT-PCR). The metabolomic profiles of SHRs pre-protected by OA were significantly different from those of unprotected SHRs. A total of 18 neurotransmitters could be confirmed as significantly altered metabolites, which were involved in tyrosine and glutamate metabolism as well as other pathways. The results showing seven key enzymes in neurotransmitter metabolism further validated the changes in the metabolic pathways. OA could effectively restore tyrosine metabolism in the striatum and hypothalamus, glutamate metabolism in the hippocampus, striatum and temporal lobe, cholinergic metabolism in the striatum, and histidine metabolism in the hypothalamus due to its inhibition of inflammatory reactions, structural damage of the neuronal cells, and increase in sedative activity. This study indicated that brain region-targeted metabolomics can provide a powerful tool to further investigate the possible mechanism of OA in EH.

Risk factors for postoperative cardiovascular morbidity after pheochromocytoma surgery: a large single center retrospective analysis.

Surgical resection is the primary treatment strategy for pheochromocytoma; however, it carries a high risk of morbidity and mortality, especially with respect to cardiovascular complications, which is the most common kinds of morbidity. The risk factors for morbidity remain unclear and require further exploration, moreover no studies focus on risk factors for cardiovascular morbidity. Herein we identified the risk factors for cardiovascular morbidity after pheochromocytoma surgery in Chinese patients. We retrospectively reviewed 262 patients who underwent unilateral surgical resection of pheochromocytoma at our center between 1 January 2007 and 31 December 2016. Patient demographics and extensive perioperative data were recorded and evaluated. Adjusted odds ratios and 95% confidence intervals were determined by multivariate logistic regression. Cut-off values and the area under the curve for continuous risk factors were calculated based on receiver operating characteristic curve analysis. A p-value <0.05 was considered statistically significant. Of the 262 patients, 63 (24.0%) had cardiovascular morbidity. The independent risk factors for cardiovascular morbidity were low body mass index, large radiographic tumor size, coronary heart disease, no preoperative crystal/colloid administration, and intraoperative hemodynamic instability; the corresponding odds ratio were 0.762 (p < 0.001), 1.208 (p = 0.010), 2.378 (p = 0.012), 2.720 (p = 0.011), and 4.764 (p = 0.001), respectively. The optimal cut-off values for body mass index and radiographic tumor size were 24.59 kg/m2 and 6.05 cm. We found that cardiovascular morbidity is common in patients after pheochromocytoma surgery. We identified five independent risk factors for cardiovascular morbidity. Identification of these risk factors may help to improve treatment strategies.

Protein-energy wasting and asymmetric dimethylarginine in peritoneal dialysis patients.

Cardiovascular (CVS) morbidity and mortality in the peritoneal dialysis patients (PD) is 10-30-fold higher than in the general population. A relatively low level of adiponectin and a higher level of leptin are important predictors of vascular complications as well as CVS events in PD patients. The asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, is an important risk factor of CVS morbidity and mortality. It is very important to establish all CVS risk factors in the PD patients to prevent CVS morbidity and mortality in this population. The aim of the study was to determine the plasma concentration of ADMA and adipokines in relation to the protein-energy wasting (PEW) in PD patients. The study was performed in 30 PD patients and in the control group which consisted of 23 healthy volunteers. Plasma levels of hsC-reactive protein, TNF, IL-6, leptin, adiponectin, oxyLDL and ADMA were measured by ELISA method in both groups. The nutritional status was determined by measuring the albumin, body mass index (BMI), the percentage of body fat (%F), lean body mass (LBM) and Subjective Global Assessment Score (SGA). The adequacy of dialysis was estimated by weekly Kt/V. In all PD patients, significantly higher levels of ADMA, leptin, oxyLDL, hsCRP and TNF in comparison to controls were observed. In contrast to well-nourished subjects, patients with PEW, in addition to increased hsCRP, showed significantly higher ADMA. PEW was associated with high levels of ADMA and hsCRP and this could probably be responsible for increased CVS risk in PD patients.

Effect of Vitamin D3 Supplement on Biochemical Markers and Blood Pressure Reading in Hypertensive patients as A secondary Prevention

Hypertension is the most significant risk factors for cardiovascular morbidity and mortality. It has two classes according to causes of the high blood pressure (Primary and Secondary). This study was intended to evaluate the potential benefit of vitamin D3 supplementation as a secondary preventive therapy for hypertensive patients. It is a prospective randomized controlled study was carried out on 40 patients visiting the Imam Al-Hussein medical city / Karbala and conducted from Sep 2016 to May 2017. The patients were allocated into group1; include 20 hypertensive patients presented with vitamin D deficiency assigned to receive conventional therapy for hypertension with vitamin D3 (100000 IU) orally every 2 weeks for 8 weeks, and group 2; include 20 hypertensive patients presented with vitamin D deficiency assigned to receive anti hypertension therapy only. Ethical committee approval and written consent of patients were obtained. Results revealed that the effect of vitamin D3 supplementation on both angiotensin II level and endogenous vitamin D levels were significantly clear regardless of age group, gender, BMI, duration of disease, and smoking status, except for systolic and diastolic blood pressure, TC, and LDL-c was affected particularly by age group and the duration of disease.

Effect of Vitamin D3 Supplement on Biochemical Markers and Blood Pressure Reading in Hypertensive patients as A secondary Prevention

Hypertension is the most significant risk factors for cardiovascular morbidity and mortality. It has two classes according to causes of the high blood pressure (Primary and Secondary). This study was intended to evaluate the potential benefit of vitamin D3 supplementation as a secondary preventive therapy for hypertensive patients. It is a prospective randomized controlled study was carried out on 40 patients visiting the Imam Al-Hussein medical city / Karbala and conducted from Sep 2016 to May 2017. The patients were allocated into group1; include 20 hypertensive patients presented with vitamin D deficiency assigned to receive conventional therapy for hypertension with vitamin D3 (100000 IU) orally every 2 weeks for 8 weeks, and group 2; include 20 hypertensive patients presented with vitamin D deficiency assigned to receive anti hypertension therapy only. Ethical committee approval and written consent of patients were obtained. Results revealed that the effect of vitamin D3 supplementation on both angiotensin II level and endogenous vitamin D levels were significantly clear regardless of age group, gender, BMI, duration of disease, and smoking status, except for systolic and diastolic blood pressure, TC, and LDL-c was affected particularly by age group and the duration of disease.

Histone lysine dimethyl-demethylase KDM3A controls pathological cardiac hypertrophy and fibrosis

Left ventricular hypertrophy (LVH) is a major risk factor for cardiovascular morbidity and mortality. Pathological LVH engages transcriptional programs including reactivation of canonical fetal genes and those inducing fibrosis. Histone lysine demethylases (KDMs) are emerging regulators of transcriptional reprogramming in cancer, though their potential role in abnormal heart growth and fibrosis remains little understood. Here, we investigate gain and loss of function of an H3K9me2 specific demethylase, Kdm3a, and show it promotes LVH and fibrosis in response to pressure-overload. Cardiomyocyte KDM3A activates Timp1 transcription with pro-fibrotic activity. By contrast, a pan-KDM inhibitor, JIB-04, suppresses pressure overload-induced LVH and fibrosis. JIB-04 inhibits KDM3A and suppresses the transcription of fibrotic genes that overlap with genes downregulated in Kdm3a-KO mice versus WT controls. Our study provides genetic and biochemical evidence for a pro-hypertrophic function of KDM3A and proof-of principle for pharmacological targeting of KDMs as an effective strategy to counter LVH and pathological fibrosis.