Major Cause Of Cardiovascular Morbidity Research Articles

Mechanistic implications of altered protein expression in rheumatic heart disease.

Rheumatic heart disease (RHD) is a major cause of cardiovascular morbidity and mortality in low- and middle-income countries, where living conditions promote spread of group A β-haemolytic streptococcus. Autoimmune reactions due to molecular mimicry of bacterial epitopes by host proteins cause acute rheumatic fever (ARF) and subsequent disease progression to RHD. Despite knowledge of the factors that predispose to ARF and RHD, determinants of the progression to valvular damage and the molecular events involved remain incompletely characterised. This review focuses on altered protein expression in heart valves, myocardial tissue and plasma of patients with RHD and pathogenic consequences on RHD. Proteins mainly involved in structural organization of the valve matrix, blood homeostasis and immune response were altered due to RHD pathogenesis. Study of secreted forms of these proteins may aid the development of non-invasive biomarkers for early diagnosis and monitoring outcomes in RHD. Valve replacement surgery, the single evidence-based strategy to improve outcomes in severe RHD, is costly, largely unavailable in low- and middle-income countries (LMIC) and requires specialised facilities. When diagnosed early, penicillin prophylaxis may be used to delay progression to severe valvular damage. Echocardiography and cardiovascular magnetic resonance and the standard imaging tools recommended to confirm early diagnosis remain largely unavailable and inaccessible in most LMIC and both require expensive equipment and highly skilled persons for manipulation as well as interpretation of results. Changes in protein expression in heart valves and myocardium are associated with progressive valvular deformation in RHD. Understanding these protein changes should shed more light on the mechanisms of pathogenicity, while secreted forms of these proteins may provide leads towards a biomarker for non-invasive early detection of RHD.

Genetically Predicted Midlife Blood Pressure and Coronary Artery Disease Risk: Mendelian Randomization Analysis.

BackgroundElevated blood pressure is a major cause of cardiovascular morbidity and mortality. However, it is not known whether midlife blood pressure affects later life cardiovascular risk independent of later life blood pressure.Methods and ResultsUsing genetic association estimates from the UK Biobank and CARDIoGRAMplusC4D consortium, univariable mendelian randomization was performed to investigate the total effect of genetically predicted mean arterial pressure (MAP) at age ≤55 years on coronary artery disease (CAD) risk, and multivariable mendelian randomization was performed to investigate the effect of genetically predicted MAP on CAD risk after adjusting for genetically predicted MAP at age >55 years. In both univariable and multivariable mendelian randomization analyses, there was consistent evidence of higher genetically predicted MAP at age ≤55 years increasing CAD risk. This association persisted after adjusting for genetically predicted MAP at age >55 years, when considering nonoverlapping populations for the derivation of MAP and CAD risk genetic association estimates, when investigating only incident CAD events after age >55 years, and when restricting the analysis to variants with most heterogeneity in their associations with MAP ≤55 and >55 years. For a 10–mm Hg increase in genetically predicted MAP at age ≤55 years, the odds ratio of later life CAD was 1.43 (95% CI, 1.16–1.77; P=0.001) after adjusting for genetically predicted MAP at age >55 years.ConclusionsThese mendelian randomization findings support a cumulative lifetime effect of elevated blood pressure on increasing CAD risk. Clinical and public health efforts toward cardiovascular disease reduction should optimize blood pressure control throughout life.

Near-Infrared Spectroscopy Intravascular Ultrasound Imaging: State of the Art.

Acute coronary syndromes (ACS) secondary to coronary vessel plaques represent a major cause of cardiovascular morbidity and mortality worldwide. Advancements in imaging technology over the last 3 decades have continuously enabled the study of coronary plaques via invasive imaging methods like intravascular ultrasound (IVUS) and optical coherence tomography (OCT). The introduction of near-infrared spectroscopy (NIRS) as a modality that could detect the lipid (cholesterol) content of atherosclerotic plaques in the early nineties, opened the potential of studying “vulnerable” or rupture-prone, lipid-rich coronary plaques in ACS patients. Most recently, the ability of NIRS-IVUS to identify patients at risk of future adverse events was shown in a prospective multicenter trial, the Lipid-Rich-plaque Study. Intracoronary NIRS-IVUS imaging offers a unique method of coronary lipid-plaque characterization and could become a valuable clinical diagnostic and treatment monitoring tool.

Study of Dyslipidemia in Iraqi Hypertension Patients in Tikrit City

Background: Hypertension is prevalent all over the world and represent a major health problem. Dyslipidemia is a major cause of cardiovascular morbidity and mortality. There is a correlation between hyperlipidemia and hypertension.Aim of study: to find out the prevalence of dyslipidemia in Iraqi hypertension patients, and to find out how many of them on statin therapy, and how many reach target according to the last guidelinesPatients and methods: a cross-sectional study conducted in outpatient clinic in Salahaddin General Hospital in Tikrit City. About 344 hypertensive patients were included in this study. A questionnaires including general information about patients were filled and venous blood was drawn from every patient and sent for hospital lab to measure necessary investigations. ASCVD risk score was calculated for every patient by ASCVD Risk Estimator Plus. Then data were analyzed by application of Microsoft excel program and Statistical Package for Social Sciences (SPSS) version 23.Results: (49%) of hypertension patients had total cholesterol of >200 mg/dl, (63.4%) had LDL of ?115 mg/dl, (57.6%) had HDL of <40 mg/dl, and (54.1%) had triglycerides of ?150mg/dl. Smoker patients in this study had highest ASCVD risk score (12.65±6.63%) followed by former smokers (7.36±3.56%) and non-smokers (6.02±4.16%).Only 76 (22.1%) of hypertension patients were on statin therapy for hyperlipidemia and only 18 (23.7%) of them reaching target LDL level according to 2016 ESC/EAS guidelines. While 268 (77.9%) of hypertension patients had no statin therapy and only 65 (24.3%) of them had LDL level within target.Conclusion: Hyperlipidemia is very prevalent in hypertension patients in Tikrit City, despite that only one of five receiving treatment and only one of four from those who received treatment reaching the target of LDL level according to 2016 ESC/EAS guidelines, and three of four of those who are on no treatment are out of the target. This is a major health problem need attention.

Arrythmia in Congenital Heart Diseases, Where Are We?

Background: Arrythmia is a major cause of cardiovascular morbidity and mortality in patients with congenital heart diseases. It has multifactorial predisposing factor as congenitally malformed or displaced conduction system, hemodynamic, mechanical or hypoxic stress and residual or postoperative sequelae. Methods: This was a prospective observational study involving all patients who were following up or referred to congenital and structural heart disease unit in our department over a period of 42 months and were discovered to have significant symptomatic cardiac arrhythmia. A detailed custom-made sheet was applied to all eligible patients to collect demographic data, underlying congenital heart disease, type of arrhythmia and possible management and/or outcome. Results: The study population included 107 patients with different congenital heart diseases with mean age 20.47+/- 13.2. Bradyarrhythmia were more common (67%) than tachyarrhythmia. Post-operative CHB was the most common bradyarrythmia. One third of the patients had atrial or ventricular tachyarrythmia. Post Fallot repair patients developed ventricular tachycardia while patients with Ebstein anomaly more commonly developed atrial tachycardias, flutter or SVT. Patients with CHB were managed with transvenous pacing (51%), epicardial pacing (16%), two patients with CCTGA with impaired RV functions underwent CRT implantation, two patients post Fallot repair underwent ICD implantation. Conclusion: Patients with CHD are subjected to wide range of arrhythmias. Postoperative complete heart block was the commonest arrhythmia in this registry especially in patients with L-TGA, AVSD and VSD. Tachyarrythmias accounted for one third of the patients. Atriotomy incisions, sutures, and conduit is a major risk factor for post-operative atrial tachycardia. The use of ICDs and CRT in patient with congenital heart diseases have proven relative efficacy.

Antiarrhythmic Properties of Ranolazine: Inhibition of Atrial Fibrillation Associated TASK-1 Potassium Channels.

Background: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and one of the major causes of cardiovascular morbidity and mortality. Despite good progress within the past years, safe and effective treatment of AF remains an unmet clinical need. The anti-anginal agent ranolazine has been shown to exhibit antiarrhythmic properties via mainly late INa and IKr blockade. This results in prolongation of the atrial action potential duration (APD) and effective refractory period (ERP) with lower effect on ventricular electrophysiology. Furthermore, ranolazine has been shown to be effective in the treatment of AF. TASK-1 is a two-pore domain potassium (K2P) channel that shows nearly atrial specific expression within the human heart and has been found to be upregulated in AF, resulting in shortening the atrial APD in patients suffering from AF. We hypothesized that inhibition TASK-1 contributes to the observed electrophysiological and clinical effects of ranolazine. Methods: We used Xenopus laevis oocytes and CHO-cells as heterologous expression systems for the study of TASK-1 inhibition by ranolazine and molecular drug docking simulations to investigate the ranolazine binding site and binding characteristics. Results: Ranolazine acts as an inhibitor of TASK-1 potassium channels that inhibits TASK-1 currents with an IC50 of 30.6 ± 3.7 µM in mammalian cells and 198.4 ± 1.1 µM in X. laevis oocytes. TASK-1 inhibition by ranolazine is not frequency dependent but shows voltage dependency with a higher inhibitory potency at more depolarized membrane potentials. Ranolazine binds within the central cavity of the TASK-1 inner pore, at the bottom of the selectivity filter. Conclusions: In this study, we show that ranolazine inhibits TASK-1 channels. We suggest that inhibition of TASK-1 may contribute to the observed antiarrhythmic effects of Ranolazine. This puts forward ranolazine as a prototype drug for the treatment of atrial arrhythmia because of its combined efficacy on atrial electrophysiology and lower risk for ventricular side effects.

Chronic treatment of curcumin improves hepatic lipid metabolism and alleviates the renal damage in adenine-induced chronic kidney disease in Sprague-Dawley rats

BackgroundChronic kidney disease (CKD), including nephrotic syndrome, is a major cause of cardiovascular morbidity and mortality. The literature indicates that CKD is associated with profound lipid disorders due to the dysregulation of lipoprotein metabolism which progresses kidney disease. The objective of this study is to evaluate the protective effects of curcumin on dyslipidaemia associated with adenine-induced chronic kidney disease in rats.MethodsMale SD rats (n = 29) were divided into 5 groups for 24 days: normal control (n = 5, normal diet), CKD control (n = 6, 0.75% w/w adenine-supplemented diet), CUR 50 (n = 6, 50 mg/kg/day curcumin + 0.75% w/w adenine-supplemented diet), CUR 100 (n = 6, 100 mg/kg/day curcumin + 0.75% w/w adenine-supplemented diet), and CUR 150 (n = 6, 150 mg/kg/day curcumin + 0.75% w/w adenine-supplemented diet). The serum and tissue lipid profile, as well as the kidney function test, were measured using commercial diagnostic kits.ResultsThe marked rise in total cholesterol, low-density lipoprotein (LDL) cholesterol, very low-density lipoprotein (VLDL) cholesterol, triglycerides and free fatty acids in serum, as well as hepatic cholesterol, triglyceride and free fatty acids of CKD control rats were significantly protected by curcumin co-treatment (at the dose of 50, 100 and 150 mg/kg). Furthermore, curcumin significantly increased the serum high-density lipoprotein (HDL) cholesterol compared to the CKD control rats but did not attenuate the CKD-induced weight retardation. Mathematical computational analysis revealed that curcumin significantly reduced indicators for the risk of atherosclerotic lesions (atherogenic index) and coronary atherogenesis (coronary risk index). In addition, curcumin improved kidney function as shown by the reduction in proteinuria and improvement in creatinine clearance.ConclusionThe results provide new scientific evidence for the use of curcumin in CKD-associated dyslipidaemia and substantiates the traditional use of curcumin in preventing kidney damage.

A Biochemical and Biophysical Investigation into the Pathological Gain-of-Function of Nitrated Hsp90

Atherosclerosis is a multifactorial chronic and inflammatory disease of medium and large arteries, and the major cause of cardiovascular morbidity and mortality worldwide. The pathogenesis of atherosclerosis involves a number of risk factors and complex events including hypercholesterolemia, endothelial dysfunction, increased permeability to low density lipoproteins (LDL) and their sequestration on extracellular matrix in the intima of lesion-prone areas. These events promote LDL modifications, particularly by oxidation, which generates acute and chronic inflammatory responses implicated in atherogenesis and lesion progression. Reactive oxygen species (ROS) (which include both free radical and non-free radical oxygen intermediates), play a key-role at each step of atherogenesis, in endothelial dysfunction, LDL oxidation, and inflammatory events involved in the initiation and development of atherosclerosis lesions. Most advanced knowledge supporting the “oxidative theory of atherosclerosis” i.e. the nature and the cellular sources of ROS and antioxidant defences, as well as the mechanisms involved in the redox balance, is based on the use of genetically engineered animals, i.e. transgenic, genetically modified, or altered for systems producing or neutralizing ROS in the vessels. This review summarizes the results obtained from animals genetically manipulated for various sources of ROS or antioxidant defences in the vascular wall, and their relevance (advance or limitation), for understanding the place and role of ROS in atherosclerosis.

Allosteric Modulation of Cytoglobin Heme Pocket Reactivity by Critical Surface Thiols – Effect of Low Hydrogen Peroxide Concentrations

Atherosclerosis is a multifactorial chronic and inflammatory disease of medium and large arteries, and the major cause of cardiovascular morbidity and mortality worldwide. The pathogenesis of atherosclerosis involves a number of risk factors and complex events including hypercholesterolemia, endothelial dysfunction, increased permeability to low density lipoproteins (LDL) and their sequestration on extracellular matrix in the intima of lesion-prone areas. These events promote LDL modifications, particularly by oxidation, which generates acute and chronic inflammatory responses implicated in atherogenesis and lesion progression. Reactive oxygen species (ROS) (which include both free radical and non-free radical oxygen intermediates), play a key-role at each step of atherogenesis, in endothelial dysfunction, LDL oxidation, and inflammatory events involved in the initiation and development of atherosclerosis lesions. Most advanced knowledge supporting the “oxidative theory of atherosclerosis” i.e. the nature and the cellular sources of ROS and antioxidant defences, as well as the mechanisms involved in the redox balance, is based on the use of genetically engineered animals, i.e. transgenic, genetically modified, or altered for systems producing or neutralizing ROS in the vessels. This review summarizes the results obtained from animals genetically manipulated for various sources of ROS or antioxidant defences in the vascular wall, and their relevance (advance or limitation), for understanding the place and role of ROS in atherosclerosis.

Chemogenetic Approaches to Redox Biology

Atherosclerosis is a multifactorial chronic and inflammatory disease of medium and large arteries, and the major cause of cardiovascular morbidity and mortality worldwide. The pathogenesis of atherosclerosis involves a number of risk factors and complex events including hypercholesterolemia, endothelial dysfunction, increased permeability to low density lipoproteins (LDL) and their sequestration on extracellular matrix in the intima of lesion-prone areas. These events promote LDL modifications, particularly by oxidation, which generates acute and chronic inflammatory responses implicated in atherogenesis and lesion progression. Reactive oxygen species (ROS) (which include both free radical and non-free radical oxygen intermediates), play a key-role at each step of atherogenesis, in endothelial dysfunction, LDL oxidation, and inflammatory events involved in the initiation and development of atherosclerosis lesions. Most advanced knowledge supporting the “oxidative theory of atherosclerosis” i.e. the nature and the cellular sources of ROS and antioxidant defences, as well as the mechanisms involved in the redox balance, is based on the use of genetically engineered animals, i.e. transgenic, genetically modified, or altered for systems producing or neutralizing ROS in the vessels. This review summarizes the results obtained from animals genetically manipulated for various sources of ROS or antioxidant defences in the vascular wall, and their relevance (advance or limitation), for understanding the place and role of ROS in atherosclerosis.

Atorvastatin Improves Hepatic Lipid Metabolism and Protects Renal Damage in Adenine-Induced Chronic Kidney Disease in Sprague-Dawley Rats.

Objective Chronic kidney disease (CKD), including nephrotic syndrome, is a major cause of cardiovascular morbidity and mortality. The literature indicates that CKD is associated with profound lipid disorders largely due to the dysregulation of lipoprotein metabolism which further aggravates the progression of kidney disease. The present study sought to determine the efficacy of atorvastatin treatment on hepatic lipid metabolism and renal tissue damage in CKD rats. Methods Serum, hepatic and faecal lipid contents and the expression and enzyme activity of molecules involved in cholesterol and triglyceride metabolism, along with kidney function, were determined in untreated adenine-induced CKD, atorvastatin-treated CKD (10 mg/kg/day oral for 24 days) and control rats. Key Findings CKD resulted in metabolic dyslipidaemia, renal insufficiency, hepatic lipid accumulation, upregulation of 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase, acyl-CoA cholesterol acyltransferase-2 (ACAT2) and the downregulation of LDL receptor protein, VLDL receptor, hepatic lipase, lipoprotein lipase (LPL), lecithin–cholesterol acyltransferase (LCAT) and scavenger receptor class B type 1 (SR-B1). CKD also resulted in increased enzymatic activity of HMG-CoA reductase and ACAT2 together with decreased enzyme activity of lipase and LCAT. Atorvastatin therapy attenuated dyslipidaemia, renal insufficiency, reduced hepatic lipids, HMG-CoA reductase and ACAT2 protein abundance and raised LDL receptor and lipase protein expression. Atorvastatin therapy decreased the enzymatic activity of HMG-CoA reductase and increased enzymatic activity of lipase and LCAT. Conclusions Atorvastatin improved hepatic tissue lipid metabolism and renal function in adenine-induced CKD rats.

A study to assess valvular heart disease in a tertiary care hospital: a single centre finding

Background: Diseases of the heart valves constitute a major cause of cardiovascular morbidity and mortality worldwide with an enormous burden on healthcare resources. The present study was undertaken to study incidence and demography of valvular heart disease, to assess echocardiography and colour doppler findings of patients with valvular heart disease and to find out complications in patients with valvular heart disease.Methods: A hospital based longitudinal case study was undertaken at medicine department of Dr. V.M. Government Medical College, Solapur, Maharashtra, India for a period of two years. One hundred and twenty-four (124) patients attending OPD participated in the study.Results: In the present study, out of 124 patients, mitral valve was most commonly involved, 105(84.67%) and the least common involved was tricuspid 1(0.81%). The most common aetiology was rheumatic origin 75(94.94%). In the present study the most common complication was pulmonary hypertension 69(55.65%), followed by congestive cardiac failure (33.87%), acute pulmonary edema (12.09%), infective endocarditis (4.84%), cerebrovascular accident (4.03%), left atrial thrombus (3.23%) and death (3.23%).Conclusions: Multiple valves were affected in more than a third of all cases, although recent research in India continue to demonstrate a declining trend in the prevalence of RHD, rheumatic involvement is still the dominant form of valvular heart disease in India.

Acute Effect of Electronic Hookah Smoking on Endothelial Function in Young Healthy Male Adults

Smoking is a major cause of cardiovascular morbidity and mortality worldwide. Over recent years, alternative forms of traditional tobacco smoking have emerged, including electronic (e‐) cigarettes and e‐hookah bowls, with claims that they are safer tobacco alternatives. Unlike e‐cigarettes, e‐hookah bowls are used through traditional water‐pipes, allowing the vapor—containing aerosolized nicotine, propylene glycol, glycerin, and flavorings—to pass through a water‐filled base, potentially altering the vapor, before it is inhaled to the user's mouth. While e‐cigarettes have been shown to cause acute endothelial dysfunction, the effect of e‐hookah is unknown. In eight overtly healthy, young, male adult hookah smokers who do not smoke cigarettes (age 25±3 years; body mass index, BMI 23.9±2.7 kg·m2 mean±SD), we measured heart rate, blood pressure and endothelial function (as measured by brachial artery flow‐mediated dilation (FMD)) before and after a 30‐minute e‐hookah smoking session. Hookah smoking increased heart rate (Δ heart rate: +10±13 beats.min−1) and blood pressure (ΔSBP: +12±7 mm Hg; ΔDBP: +8±5 mm Hg). Importantly, after e‐hookah smoking, FMD decreased from 6.59 ± 2.61 to 5.33 ± 1.97 %Δ, indicating impaired endothelial function. As functional impairment of the endothelium is one of the first recognizable signs of development of atherosclerosis, this new preliminary data provide an initial line of scientific evidence to counter claims that smoking e‐hookah is a safe tobacco alternative. Future studies are indicated to elucidate the long‐term effects of e‐hookah smoking on vascular health, which overtime could accelerate the development of cardiovascular diseases.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Histopathologic Characterization of Peripheral Arteries in Subjects With Abundant Risk Factors: Correlating Imaging With Pathology

ObjectivesThe aim of this study was to comprehensively evaluate the pathology of the lower extremity arteries across their entire length in subjects dying with abundant risk factors and to evaluate the clinical and imaging implications of the pathological characteristics. BackgroundLower extremity peripheral arterial disease is a major cause of cardiovascular morbidity, but a systematic characterization of the pathology has never been undertaken. MethodsTwelve legs were obtained from 8 cadavers with histories of coronary risk factors (median age 82 years, 6 men); 8 of 12 legs were evaluated using computed tomography before the major peripheral arteries were dissected along their entire length. Dissected arteries were cut serially at 3 to 4 mm, and a total of 2,987 sections were examined. ResultsLuminal irregularities and stenosis were more commonly seen in computed tomography images of above-the-knee (AK) arteries. Atherosclerotic lesions were histologically confirmed and were more common in AK (95.7%) than below-the-knee (BK) (56.8%) arteries. Occluded vessels were observed at 18 sites, including 8 AK and 10 BK arteries. Pathologically, acute thrombus was observed in all 8 AK sites, of which 3 were associated with plaque rupture and 5 were related to calcified nodules. The 10 occluded BK arteries revealed chronic total occlusions, of which one-half were embolic in origin and one-half were associated with atherosclerotic lesions. Intimal (75.3%) and medial (86.2%) calcifications were commonly encountered. Proportionate to the neointimal atherosclerosis, intimal calcification was more severe in AK arteries; the severity of medial calcification was no different between AK and BK arteries. Calcification was significantly greater in arteries excised from subjects with compared with those without diabetes. ConclusionsAtherosclerosis occurs more commonly in AK arteries and luminal occlusion from acute thrombosis secondary to rupture or calcified nodules. BK occlusion was chronic in nature, and at least one-half of lesions were embolic in origin. Medial calcification was similarly common in AK and BK arteries but more prevalent in subjects with diabetes.

Dysregulated IL-1β-GM-CSF Axis in Acute Rheumatic Fever That Is Limited by Hydroxychloroquine.

Acute rheumatic fever (ARF) and rheumatic heart disease are autoimmune consequences of group A streptococcus infection and remain major causes of cardiovascular morbidity and mortality around the world. Improved treatment has been stymied by gaps in understanding key steps in the immunopathogenesis of ARF and rheumatic heart disease. This study aimed to identify (1) effector T cell cytokine(s) that might be dysregulated in the autoimmune response of patients with ARF by group A streptococcus, and (2) an immunomodulatory agent that suppresses this response and could be clinically translatable to high-risk patients with ARF. The immune response to group A streptococcus was analyzed in peripheral blood mononuclear cells from an Australian Aboriginal ARF cohort by a combination of multiplex cytokine array, flow cytometric analysis, and global gene expression analysis by RNA sequencing. The immunomodulatory drug hydroxychloroquine was tested for effects on this response. We found a dysregulated interleukin-1β-granulocyte-macrophage colony-stimulating factor (GM-CSF) cytokine axis in ARF peripheral blood mononuclear cells exposed to group A streptococcus in vitro, whereby persistent interleukin-1β production is coupled to overproduction of GM-CSF and selective expansion of CXCR3+CCR4-CCR6- CD4 T cells. CXCR3+CCR4-CCR6- CD4 T cells are the major source of GM-CSF in human CD4 T cells and CXCL10, a CXCR3 ligand and potent T helper 1 chemoattractant, was elevated in sera from patients with ARF. GM-CSF has recently emerged as a key T cell-derived effector cytokine in numerous autoimmune diseases, including myocarditis, and the production of CXCL10 may explain selective trafficking of these cells to the heart. We provide evidence that interleukin-1β amplifies the expansion of GM-CSF-expressing CD4 T cells, which is effectively suppressed by hydroxychloroquine. RNA sequencing showed shifts in gene expression profiles and differentially expressed genes in peripheral blood mononuclear cells derived from patients at different clinical stages of ARF. Given the safety profile of hydroxychloroquine and its clinical pedigree in treating autoimmune diseases such as rheumatoid arthritis, where GM-CSF plays a pivotal role, we propose that hydroxychloroquine could be repurposed to reduce the risk of rheumatic heart disease after ARF.

Prevalence and patterns of coronary artery disease in patients undergoing cardiac surgery for rheumatic and non- rheumatic valvular heart disease in a tertiary care center of Nepal

Background and Aims: Coronary artery disease (CAD) constitute a major cause of cardiovascular morbidity and mortality worldwide with an enormous burden on healthcare resources. Prevalence and pattern of CAD in patients of rheumatic and non-rhemuatic valvular heart diseases varies widely with limited data on optimal strategies for diagnosis and treatment.Methods: This study includes 97 patients with rheumatic and non-rheumatic valvular heart disease who underwent coronary angiogram (CAG) before cardiac surgery. Patients were divided into two groups based on rheumatic heart disease (RHD) &amp; non-rheumatic disease (Non-RHD) and correlate the patterns of CAD.Results: Out of 97 patients, 22 (22.6%) patients were found to have significant CAD. In patients with non-rheumatic origin CAD was common (15 patients, 68.1%) as compared to rheumatic origin (7 patients, 31. 8%). In rheumatic origin, the prevalence was 7(12.2%) out of 57 patients while in non-rheumatic origin, was 15(37.5%) out of 40 patients. In RHD group, all patients with CAD were found to have single vessel diease (SVD) while, in non-RHD group, 11 patients (73.3%) had SVD, 3 patients (16.7%) had double vessel disease (DVD) and one patient (5.6%) had triple vessel disease (TVD).Conclusions: Prevalence of CAD is higher in patients with non-RHD in comparison to those with RHD. We also found SVD to be the most common pattern of CAD in both rheumatic and non-rheumatic valvular heart disease.

A11389 White collared people and housewives are carrying high risk with undetected hypertension in India

Objectives: 53705 individuals of more than 18 years of age after taking due consent,were screened for their blood pressure. Targeted population included those who have not measured their blood pressure in last one year. We measured their blood pressure with the intention to know undetected hypertension among apparently healthy population at 104 centers across India. Methods: Omron electronic BP instrument has been used to measure blood pressure. Two readings has been taken and second one is recorded in data sheet which was approved of Independent ethics committee. People have been approached by door to door survey. Results: 48436 people had not measured their blood pressure for last one year. 56.9% were male. 17.8% of them found hypertensive while this percentage among females was 8.25% only. Only 24.4% people who have been detected with hypertension were aware about hypertension. Overall prevalence of hypertension in those who were not measured their blood pressure in last one year was 13.69%. This undetected hypertension has been most common in elderly age group above 55 years i.e. 32.16% who were otherwise healthy and not knowing about their hypertension. People between 35 to 55 years of age had 16.65% undetected hypertension and among those having less than 35 years of age, it was 4.82%. Biggest percentage of this hidden hypertension was among white collared 33.38% followed by blue collared having 19.86% and housewives having 19.73% with no statistical difference. Conclusion: white collared people and housewives are on higher risk of hypertension. As it is major cause of cardiovascular morbidity and mortality, it is important to keep a record of blood pressure of every individuals so that they can be prevented of dreaded outcomes. Awareness drive should also be run.

Pleural effusion as an indicator of short term mortality in acute pulmonary embolism.

Pulmonary embolism (PE) is known as one of the major causes of cardiovascular morbidity and mortality. Identification of high risk patients for short term and long-term mortality is crucial. The purpose of this study is to demonstrate the prognostic importance of simplified pulmonary embolism severity index (sPESI), radiological investigations and comorbidities in terms of short-term mortality by simultaneous assessment of sPESI score, pulmonary computed tomography (CT) angiography findings and underlying comorbidities in patients diagnosed with acute pulmonary embolism. We retrospectively evaluated 570 patients diagnosed with acute PE confirmed by computer tomography pulmonary angiography (CTPA). Comorbidities were recorded, pulmonary embolism severity index scores were calculated and CTPA data were evaluated as predictors for short-term mortality. The study population consisted of 570 patients, 292 (51.2%) patients were female and 74 patients (12.9%) died within 30 days due to PE diagnosis. In univariate analysis male gender (p= 0.031), congestive heart failure (CHF)(p< 0.029), main pulmonary artery involvement (p= 0.045), presence of pleural effusion (p= 0.001) and pericardial effusion (p= 0.004) at time of diagnosis and high risk sPESI group (p< 0.001) had a significant influence on mortality. In the multivariate analysis, pleural effusions (HR, 1.67; CI, 1.05-2.66; p< 0.030) and sPESI high risk group (HR, 9.56; CI, 4.71-19.43; p< 0.001) were remained significant and independent prognostic factors for survival. The present study underlined that presence of pleural effusion at the time of diagnosis in patients with massive pulmonary embolism and a high sPESI score in other patients were significant predictors of short-term mortality.

Cardiovascular Effects of Hookah Smoking: Potential Implications for Cardiovascular Risk.

Smoking is a major cause of cardiovascular morbidity and mortality worldwide. Hookah (ie, waterpipe) smoking is a centuries-old revived yet understudied global epidemic of tobacco use. Because of the traditional set-up of a hookah-pipe, in addition to inhaling tobacco-combustion products, smokers are also exposed to large amounts of charcoal combustion products from the burning charcoal briquettes used to heat the hookah flavored tobacco. Despite being heavily advertised and actively glamorized in the mass media as a healthier tobacco alternative, the toxicological constituents of hookah smoke-including nicotine, carbon monoxide, particulates, oxidants, heavy metals, phenols and flavorants-indicate the potential to cause adverse cardiovascular events. Herein, we review evidence on hookah smoke toxicological constituents, cardiovascular effects and potential mechanisms by which hookah smoke aerosol could cause cardiovascular disease. The evidence reviewed here indicates that contrary to the widespread popular belief that hookah is a healthier tobacco alternative, the constituents of hookah smoke aerosol contains similar chemicals compared to cigarette smoke, many of which are known to be harmful to cardiovascular health and mediated by similar pathophysiologic processes. Because the burning charcoal briquettes are a unique source of toxicant emissions specific to hookah smoking, some constituents differ in their quantities from cigarettes with some of their cardiovascular effects unknown. To date, much more is known about the constituents and their toxicology than about the effects of hookah smoking on human cardiovascular health. Further research on long-term consequences of hookah use is needed. This review provides an overview on the potential impact of hookah smoking on cardiovascular health. Readers will gain an insight into evidence on its toxicological constituents, human health effects, and pathophysiological mechanisms by which hookah smoking might cause cardiovascular disease. The review also highlights current research gaps regarding the cardiovascular consequences of hookah smoking, specifically the long-term consequences in the United States and Europe among flavored-hookah tobacco users.

Anti-endothelial cell antibody rich sera from rheumatic heart disease patients induces proinflammatory phenotype and methylation alteration in endothelial cells

Rheumatic heart disease (RHD) is a major cause of cardiovascular morbidity and mortality in developing nations like India. RHD commonly affects the mitral valve which is lined by a single layer of endothelial cells (ECs). The role of ECs in mitral valve damage during RHD is not well elucidated. In here, anti-endothelial cell antibody from RHD patients has been used to stimulate the ECs (HUVECs and HMVECs). ECs proinflammatory phenotype with increased expression of TNFα, IL-6, IL-8, IFNγ, IL-1β, ICAM1, VCAM1, E-selectin, laminin B, and vimentin was documented in both ECs. The promoter hypomethylation of various key inflammatory cytokines (TNFα, IL-6, and IL-8), integrin (ICAM1) associated with leukocyte transendothelial migration, and extracellular matrix genes (vimentin, and laminin) were also observed. Further, the in-vitro data was in accordance with ex-vivo observations which correlated significantly with the etiological factors such as smoking, socioeconomic status, and housing. Thus, the study sheds light on the role of ECs in RHD which is a step forward in the elucidation of disease pathogenesis.