Major Cause Of Cardiovascular Morbidity Research Articles

Abstract P373: A Cohort Study in Elderly Population - Differences Between Older and Very Older Subjects

Introduction: It is known that isolated systolic hypertension (ISH) and elevated pulse pressure (PP) play an important role in the development of cerebrovascular disease, congestive heart failure, and coronary heart disease, which are the major causes of cardiovascular morbidity and mortality in the population aged older than 65 years. The systolic blood pressure (BP) has been proven to be a stronger predictor of cardiovascular diseases than diastolic BP and a correlation between mortality and high BP has been extensively proven for those in late life until around the age of 80 years. Objective: To evaluate BP profile on 24-hour, daytime and night time periods, pulse pressure (PP), riser BP pattern and systolic and diastolic nocturnal drop in an elderly population, referred to be clinically healthy with no prior history of CV disease and off CV medications. Methods: We analyzed a cohort of 1300 elderly patients aged over 65 years and compared the ambulatory blood pressure data of elderly individuals (G1) aged 65-79 years (1020 subjects, mean 67.16 years, 64.7% female) and very elderly individuals (G2) aged over 80 years (280subjects, mean 83.89 years, 69.3% female). Results: Differing trends for systolic and diastolic BP between groups resulted in large differences in ambulatory PP, it being significantly greater ( p = 0.001) throughout the entire 24-hour in G2, even after correcting for age (24-hour, daytime and night time periods being 55,07 x 66,76mmHg, 55,31 x 67,03mmHg and 54,55 x 65,95mmHg , respectively in G1 and G2). The prevalence of non-dipping was not significantly higher in G2. Largest difference between groups was in the prevalence of the riser BP pattern, asleep systolic BP mean greater than awake SBP mean (18,7% vs. 6,5% in patients G2 and G1, respectively; p 0.001). Conclusions: There is a growing recognition of the importance of the systolic component of BP. About 65% of hypertension in the elderly is ISH, and CVD risk increases with PP, which is not simply a marker for stiff diseased arteries; elevated PP and asleep systolic BP mean was the major basis for the diagnosis and stratification of ISH.

Repetitive ROS Inhibits Nrf2 Antioxidant Defense in Ischemic Heart Failure

Nrf2, the master regulator for the antioxidant response, is critical for protecting the heart against reactive oxygen species (ROS). Normally, Nrf2 is bound to Kelch‐like ECH‐associated protein 1 (Keap1) and ubiquitinated in the cytosol. With increased oxidative stress, Nrf2 is released from Keap1, and moves into nucleus, binding to the antioxidant response element (ARE) in target gene promoters. This results in increased expression of antioxidant genes. Ischemic heart failure (IHF), a major cause of cardiovascular morbidity and mortality, is an inflammatory, chronic disease characterized by increased oxidative stress and progressive loss of ventricular function; however, we found Nrf2 expression was decreased by 50% in this disease. The interesting question is does Nrf2 inactivation with corresponding failure of antioxidant response contribute to the progression of IHF? We hypothesized that repetitive ROS exposure in IHF results in depression of Nrf2 activity, which as Nrf2 also regulates its own expression will in turn lead to decreased Nrf2. H2O2 is a major contributor to oxidative stress and damage thus is ideal to investigate the circumstances that occur in vivo due to ROS. Repetitive ROS treatments (modeling the chronic condition) reduced Nrf2 levels by 50% compared to a single treatment. In experiments with isolated rat adult cardiac myocytes treated with repetitive ROS treatments, immunohistochemistry revealed Nrf2 failed to traffic to the nucleus. Downregulation of Nrf2 in IHF and in isolated adult cardiac myocytes after repetitive ROS treatment was associated with decreased Nrf2 nucleus binding activity, suggesting inhibition of the Nrf2 mediated antioxidant defense. Further work evaluated changes in gene expression and mitochondrial function with the reduction of Nrf2.Support or Funding InformationThis work was supported by the following: APS Undergraduate Research Fellowship (UGSRF); NIH RO1 HL079071; VA, Merit Review, 5101BX000839; and NIH R01 HL085844.

Did we overcome rheumatic heart disease or is it still a public disease burden?

Rheumatic heart disease (RHD), affecting approximately 32 million people all over the world is one of the major causes of cardiovascular morbidity and mortality especially in developing countries. In this ongoing pilot study, we aim to investigate the prevalence of both definitive and borderline RHD in Turkey as a developing country. A total of 386 healthy young individuals (45 female, 341 males) who applied to our Cardiology Clinic for being military personnel coming from different regions of Turkey in the year 2015, were recruited for our study. 2012 World Heart Federation (WHF) criteria for echocardiographic assessment and diagnosis of RHD were used. Study population was classified into one of the three groups as normal, borderline RHD and definitive RHD. The three groups were similar in terms of baseline characteristics and laboratory findings. Definitive and borderline RHD were found in 11 (2,9%) and 29 (7,5%) individuals, respectively. Abnormal thickening of the anterior mitral valve leaflet (AMVL) was found statistically significant between the normal and the RHD groups (3.1±0.6 vs 4.2±0.9, p

The Role of Biologically Active Ingredients from Natural Drug Treatments for Arrhythmias in Different Mechanisms.

Arrhythmia is a disease that is caused by abnormal electrical activity in the heart rate or rhythm. It is the major cause of cardiovascular morbidity and mortality. Although several antiarrhythmic drugs have been used in clinic for decades, their application is often limited by their adverse effects. As a result, natural drugs, which have fewer side effects, are now being used to treat arrhythmias. We searched for all articles on the role of biologically active ingredients from natural drug treatments for arrhythmias in different mechanisms in PubMed. This study reviews 19 natural drug therapies, with 18 active ingredient therapies, such as alkaloids, flavonoids, saponins, quinones, and terpenes, and two kinds of traditional Chinese medicine compound (Wenxin-Keli and Shensongyangxin), all of which have been studied and reported as having antiarrhythmic effects. The primary focus is the proposed antiarrhythmic mechanism of each natural drug agent. Conclusion. We stress persistent vigilance on the part of the provider in discussing the use of natural drug agents to provide a solid theoretical foundation for further research on antiarrhythmia drugs.

Mortality Due to Rheumatic Heart Disease in Developing World: A Preventable Problem

Background: Rheumatic heart disease (RHD) has been a major cause of cardiovascular morbidity and mortality in underdeveloped and developing countries, since this disease has been identified. Its prevalence has significantly come down in developed countries but this still remains an important cause of cardiovascular morbidity and mortality of younger age group in underprivileged world. The most important fact associated with this condition is, this is a preventable problem and a lot of morbidity and mortality can be avoided with proper preventive measures. Objective: This study was conducted to know one year mortality with RHD in Indira Gandhi Institute of cardiology Patna, one of the largest referral cardiac centers of of northern India, to estimate the disease burden of this preventable problem in this province. Methods and Results: A retrospective study of medical records was done for the patients died during year 2013, with rheumatic heart disease at Indira Gandhi Institute of Cardiology, Patna. This tertiary cardiac center in northern India witnessed a total of 120 deaths with RHD during the year 2013. Conclusion: 120 deaths due to RHD in a year in a referral cardiac center of northern India is significant and points towards the disease burden of this preventable problem in the province.

OP.8D.02] FIRST IN MAN TREATMENT OF SEVERE BP VARIABILITY WITH BAROREFLEX ACTIVATION THERAPY

Objective:Profound BP variability (BPV) is a major cause of cardiovascular morbidity and poor quality of life as there are no optimal pharmacological strategies to help patients. We hypothesised that in a patient with baroreflex dysfunction and preserved efferent baroreflex pathway, carotid sinus st

PS 02-08 Elevated Arterial Stiffness is Associated with Early Bone Loss in Healthy Subjects

Objective: Both arterial stiffness and osteoporosis are the major causes of cardiovascular morbidity and mortality as well as age-related public health issues. We investigated the relationship between brachial-ankle pulse wave velocity (baPWV) for arterial stiffness and bone mineral density (BMD) for osteoporosis in healthy subjects. Design and Method: Participants in this study included 1,727 subjects (mean age: 55 ± 10 years, M:F = 914:813) who underwent routine health check-up between March 2009 and August 2011. We estimated baPWV using an automated oscillometric analyzer and BMD using dual energy x-ray absorptiometry and analyzed the gender difference after categorizing the subjects into 3 groups (normal, osteopenia, and osteoporosis) according to the World Health Organization (WHO) diagnostic classification. Results: There was a significant inverse correlation and gender difference between total BMD measured in the femur and right baPWV in both male (r = −0.136, p = 0.001) and female (r = −0.234, p < 0.001), respectively. In subgroup analysis according to the WHO diagnostic classification, there was a significant gender difference of right baPWV in normal (M:F = 1437 ± 203: 1309 ± 182 cm/sec, p < 0.001) and osteopenia group (M:F = 1508 ± 296: 1428 ± 243 cm/sec, p = 0.002), respectively. However, there was no gender difference in the osteoporosis group (1550 ± 316: 1570 ± 327 cm/sec, p = 0.616). After adjusting for age and gender, right baPWV was independently associated with osteopenia (Mvs.F = odds ratio (OR):1.003, 95% confidence interval(CI) 1.002-1.004, p < 0.001 vs. OR:1.003, 95%CI 1.001-1.009, p = 0.029, respectively) and osteoporosis (Mvs.F = OR:1.002, 95%CI 1.001-1.003, p < 0.001 vs. OR:1.005, 95%CI 1.001-1.009, p = 0.010, respectively) in both male and female, respectively. Conclusions: Arterial stiffness is elevated even in the osteopenia. Therefore more specific therapeutic strategies are important for pathophysioloic understanding of vascular damage during early bone loss period.

OS 36-04 KRUPPEL LIKE FACTOR 15 IS ASSOCIATED WITH CARDIAC HYPERTROPHY IN AN EXPERIMENTAL MODEL OF KIDNEY DISEASE

Objective: Left ventricular hypertrophy (LVH) is prevalent in chronic kidney disease (CKD) and a major cause of cardiovascular morbidity and mortality. Treatment of LVH in CKD is based on blood pressure control. The Kruppel like factor 15 (KLF15) is expressed in the heart and acts as a repressor of cardiac hypertrophy and fibrosis. The role of cardiac KLF15 in the development of LVH in rats with CKD secondary to subtotal nephrectomy (STNx) or the effects of ACE inhibition on KLF15 levels has not been addressed previously. Design and Method: Female Sprague Dawley rats underwent STNx and were treated for 4 weeks with either vehicle or the ACE inhibitor ramipril (oral 1mg/kg). Control rats received vehicle (all groups, n = 8/gp). Blood pressure and cardiac function were measured by catheterisation of the left ventricle. Results: STNx rats were hypertensive (P < 0.05) with LVH and diastolic dysfunction, and had increased interstitial and perivascular fibrosis (all P < 0.05). STNx rats had significantly reduced cardiac KLF15 gene and protein expression (P < 0.05). In STNx (vs. STNx-vehicle), ramipril reduced blood pressure (P < 0.01), improved LVH and perivascular fibrosis (P < 0.01) and increased cardiac KLF15 protein (P < 0.05) but did not significantly reduce interstitial fibrosis. Conclusions: This is the first report that cardiac KLF15 is down regulated in LVH associated with CKD. ACE inhibition increased KLF15 and reduced LVH but it had no effect on interstitial fibrosis. Studies are now needed to investigate new approaches that lead to further increases in KLF15 and reduce the adverse effects of LVH in CKD.

NEAT HFpEF: Organic nitrates fail to deliver.

Heart failure with preserved ejection fraction (HFpEF) has emerged as a major cause of cardiovascular morbidity and mortality in last decades.1 The incidence of HFpEF continues to rise and currently it accounts for approximately half of all patients with HF, with morbidity, mortality, and health care costs on par with HF with reduced EF (HFrEF).1,2 HFpEF remains among the most challenging of clinical syndromes for the clinician and scientist, with a multitude of proposed mechanisms involving the heart and other organs and complex interplay with common co-morbidities.2 Unfortunately and to date, there is no effective form of therapy for such patients. The therapeutic picture for HFpEF has been less favorable than HFrEF. Other than an emphasis on rigorous control of hypertension, atrial fibrillation, and fluid retention, there is relatively little new that can be offered to those patients. Regular exercise is one of the few interventions which may offer modest improvement in peak exercise capacity in such patients – as evident in the PARIS study.3 The apparent failure of pharmacotherapy stems from the fact that HFpEF can be multifactorial and the molecular pathways remain largely undefined.

Heart failure-potential new targets for therapy.

Heart failure is a major cause of cardiovascular morbidity and mortality. This review covers current heart failure treatment guidelines, emerging therapies that are undergoing clinical trial, and potential new therapeutic targets arising from basic science advances. A non-systematic search of MEDLINE was carried out. International guidelines and relevant reviews were searched for additional articles. Angiotensin-converting enzyme inhibitors and beta-blockers are first line treatments for chronic heart failure with reduced left ventricular function. Treatment strategies to improve mortality in heart failure with preserved left ventricular function are unclear. Many novel therapies are being tested for clinical efficacy in heart failure, including those that target natriuretic peptides and myosin activators. A large number of completely novel targets are also emerging from laboratory-based research. Better understanding of pathophysiological mechanisms driving heart failure in different settings (e.g. hypertension, post-myocardial infarction, metabolic dysfunction) may allow for targeted therapies. Therapeutic targets directed towards modifying the extracellular environment, angiogenesis, cell viability, contractile function and microRNA-based therapies.

Modifiable risk factors of hypertension: A hospital-based case-control study from Kerala, India

Introduction:Hypertension is a major cause of cardiovascular morbidity and mortality in Kerala. Excess dietary salt, low dietary potassium, overweight and obesity, physical inactivity, excess alcohol, smoking, socioeconomic status, psychosocial stressors, and diabetes are considered as modifiable risk factors for hypertension.Objectives:To estimate and compare the distribution of modifiable risk factors among hypertensive (cases) and nonhypertensive (controls) patients and to estimate the effect relationship of risk factors.Materials and Methods:Age- and sex-matched case–control study was conducted in a tertiary care hospital in Kerala using a pretested interviewer-administered structured questionnaire based on the WHO STEPS instrument for chronic disease risk factor surveillance. Bivariate and multiple logistic regression analyses were done.Results:A total of 296 subjects were included in the study. The mean age of study sample was 50.13 years. All modifiable risk factors studied vis-ΰ-vis obesity, lack of physical activity, inadequate fruits and vegetable intake, diabetes, smoking, and alcohol use were significantly different in proportion among cases and controls. Obesity, lack of physical activity, smoking, and diabetes were found to be significant risk factors for hypertension after adjusting for other risk factors.Conclusion:Hypertension is strongly driven by a set of modifiable risk factors. Massive public awareness campaign targeting risk factors is essential in controlling hypertension in Kerala, especially focusing on physical exercise and control of diabetes, obesity, and on quitting smoking.

Outcome in Heart Failure with Preserved Ejection Fraction: The Role of Myocardial Structure and Right Ventricular Performance.

BackgroundHeart failure with preserved ejection fraction (HFpEF) is recognized as a major cause of cardiovascular morbidity and mortality. Thus, a profound understanding of the pathophysiologic changes in HFpEF is needed to identify risk factors and potential treatment targets in this specific patient population. Therefore, we aimed to comprehensively assess the impact of left- and right-ventricular function and hemodynamics on long-term mortality and morbidity in order to improve risk prediction in patients with HFpEF.Methods and ResultsWe prospectively included 142 consecutive patients with HFpEF into our observational, non-interventional registry. Echocardiography, cardiac magnetic resonance imaging and invasive hemodynamic assessments including myocardial biopsy were performed at baseline. We detected significant correlations between left ventricular extracellular matrix and left ventricular end-diastolic diameter (r = -0.64;p = 0.03) and stroke volume (r = -0.53;p = 0.04). Hospitalization for heart failure and/or cardiac death was observed over a median follow up of 10 months. The strongest risk factors were reduced right ventricular function (adj. HR 6.62;95%CI 3.12- 14.02;p<0.001), systolic pulmonary arterial pressure (adj. HR per 1-SD 1.55;95%CI 1.15- 2.09;p = 0.004) and the pulmonary artery wedge pressure (adj. HR per 1-SD 1.51;95%CI 1.09–2.08; p = 0.012). The area under the ROC curve for right ventricular function was 0.63, for systolic pulmonary arterial pressure 0.75, and for pulmonary artery wedge pressure 0.68.ConclusionThe current study emphasizes the importance of right ventricular function and pulmonary pressures on outcome in patients with HFpEF providing pathophysiological insights into the hemodynamic changes in HFpEF.

Targeting chromatin remodeling to prevent cardiovascular disease in diabetes.

Diabetes is a major cause of cardiovascular morbidity and mortality and its prevalence is rapidly increasing worldwide. Despite clear advances in developing effective glucose-lowering drugs, clinical trials have recently shown that intensive glycemic control failed to reduce cardiovascular events in the diabetic population. These findings support the concept that the hyperglycemic environment may be remembered in the cardiovascular system. This phenomenon has been recently defined as "metabolic memory" and may contribute to explain the progression of diabetic vascular complications despite achievement of target HbA1c levels. In this regard, epigenetic changes of DNA/histone complexes are emerging as important modulators of oxidant and inflammatory genes, thus leading to persistent cardiac and vascular dysfunction. Over the last few years, the rapid development of many compounds (i.e. histone deacetylase and histone acetyltransferase inhibitors) able to erase adverse chromatin signatures led to the perception that reverting hyperglycemic damage might be possible and represents an attractive challenge. Here we critically discuss recent evidence supporting the concept that chromatin alterations are key drivers of cardiovascular disease and describe the emerging potential of chromatin modifying agents for the reprogramming of detrimental epigenetic signatures in patients with cardiometabolic disturbances.

Effect of screening for coronary artery disease using CT angiography on mortality and cardiac events in high-risk patients with diabetes: the FACTOR-64 randomized clinical trial.

Coronary artery disease (CAD) is a major cause of cardiovascular morbidity and mortality in patients with diabetes mellitus, yet CAD often is asymptomatic prior to myocardial infarction (MI) and coronary death. To assess whether routine screening for CAD by coronary computed tomography angiography (CCTA) in patients with type 1 or type 2 diabetes deemed to be at high cardiac risk followed by CCTA-directed therapy would reduce the risk of death and nonfatal coronary outcomes. The FACTOR-64 study was a randomized clinical trial in which 900 patients with type 1 or type 2 diabetes of at least 3 to 5 years' duration and without symptoms of CAD were recruited from 45 clinics and practices of a single health system (Intermountain Healthcare, Utah), enrolled at a single-site coordinating center, and randomly assigned to CAD screening with CCTA (n = 452) or to standard national guidelines-based optimal diabetes care (n = 448) (targets: glycated hemoglobin level <7.0%, low-density lipoprotein cholesterol level <100 mg/dL, systolic blood pressure <130 mm Hg). All CCTA imaging was performed at the coordinating center. Standard therapy or aggressive therapy (targets: glycated hemoglobin level <6.0%, low-density lipoprotein cholesterol level <70 mg/dL, high-density lipoprotein cholesterol level >50 mg/dL [women] or >40 mg/dL [men], triglycerides level <150 mg/dL, systolic blood pressure <120 mm Hg), or aggressive therapy with invasive coronary angiography, was recommended based on CCTA findings. Enrollment occurred between July 2007 and May 2013, and follow-up extended to August 2014. The primary outcome was a composite of all-cause mortality, nonfatal MI, or unstable angina requiring hospitalization; the secondary outcome was ischemic major adverse cardiovascular events (composite of CAD death, nonfatal MI, or unstable angina). At a mean follow-up time of 4.0 (SD, 1.7) years, the primary outcome event rates were not significantly different between the CCTA and the control groups (6.2% [28 events] vs 7.6% [34 events]; hazard ratio, 0.80 [95% CI, 0.49-1.32]; P = .38). The incidence of the composite secondary end point of ischemic major adverse cardiovascular events also did not differ between groups (4.4% [20 events] vs 3.8% [17 events]; hazard ratio, 1.15 [95% CI, 0.60-2.19]; P = .68). Among asymptomatic patients with type 1 or type 2 diabetes, use of CCTA to screen for CAD did not reduce the composite rate of all-cause mortality, nonfatal MI, or unstable angina requiring hospitalization at 4 years. These findings do not support CCTA screening in this population. clinicaltrials.gov Identifier: NCT00488033.

Calcium-activated potassium channels in ischemia reperfusion: a brief update.

Ischemia and reperfusion (IR) injury constitutes one of the major causes of cardiovascular morbidity and mortality. The discovery of new therapies to block/mediate the effects of IR is therefore an important goal in the biomedical sciences. Dysfunction associated with IR involves modification of calcium-activated potassium channels (KCa) through different mechanisms, which are still under study. Respectively, the KCa family, major contributors to plasma membrane calcium influx in cells and essential players in the regulation of the vascular tone are interesting candidates. This family is divided into two groups including the large conductance (BKCa) and the small/intermediate conductance (SKCa/IKCa) K+ channels. In the heart and brain, these channels have been described to offer protection against IR injury. BKCa and SKCa channels deserve special attention since new data demonstrate that these channels are also expressed in mitochondria. More studies are however needed to fully determine their potential use as therapeutic targets.

Psoriasis and risk of heart failure: a nationwide cohort study.

Psoriasis is a common inflammatory disease that is associated with increased risk of cardiovascular disease, including myocardial infarction. Heart failure (HF) is independently associated with several cardiovascular risk factors and is a major cause of cardiovascular morbidity and mortality. The association between psoriasis and HF is unclear and we therefore investigated the risk of new-onset HF in a nationwide cohort of psoriasis patients compared with the background population. The study included the entire Danish population aged ≥18 years followed from 1 January 1997 until HF, death or 31 December 2011. Information on comorbidity and concomitant medication was identified by individual-level linkage of administrative registers. New-onset HF was defined as first hospital admission for HF. Incidence rates of new-onset HF were calculated and adjusted hazard ratios were estimated by multivariable Cox regression models adjusted for age, gender, comorbidity and cardiovascular medications. A total of 5 485 856 subjects were eligible for analysis. In the study period 66 389 patients with new-onset psoriasis, including 11 242 patients with severe psoriasis, were identified. The overall incidence rates of new-onset HF were 2.82, 4.22 and 4.70 per 1000 person-years for the reference population, mild psoriasis and severe psoriasis, respectively. Compared with the reference population, the fully adjusted hazard ratios for new-onset HF were increased in patients with psoriasis with a hazard ratio 1.22 (95% confidence interval 1.16-1.29) and hazard ratio of 1.53 (95% confidence interval 1.34-1.74) for those with mild and severe disease, respectively. In this nationwide cohort, psoriasis was associated with a disease severity-dependent increased risk of new-onset HF.

Incidence and patterns of valvular heart disease in a tertiary care high-volume cardiac center: a single center experience.

Diseases of the heart valves constitute a major cause of cardiovascular morbidity and mortality worldwide with rheumatic heart disease (RHD) being the dominant form of valvular heart disease (VHD) in developing nations. The current study was undertaken at a tertiary care cardiac center with the objective of establishing the incidence and patterns of VHD by Echocardiography (Echo). Among the 136,098 first-time Echocardiograms performed between January 2010 and December 2012, an exclusion criterion of trivial and functional regurgitant lesions yielded a total of 13,289 cases of organic valvular heart disease as the study cohort. In RHD, the order of involvement of valves was mitral (60.2%), followed by aortic, tricuspid and pulmonary valves. Mitral stenosis, predominantly seen in females, was almost exclusively of rheumatic etiology (97.4%). The predominant form of isolated MR was rheumatic (41.1%) followed closely by myxomatous or mitral valve prolapse (40.8%). Isolated AS, more common in males, was the third most common valve lesion seen in 7.3% of cases. Degenerative calcification was the commonest cause of isolated AS (65.0%) followed by bicuspid aortic valve (BAV) (33.9%) and RHD (1.1%). Multiple valves were involved in more than a third of all cases (36.8%). The order of involvement was MS+MR>MS+AR>MR+AR>AS+AR>MR+AS>MS+AS. Overall, 9.7% of cases had organic tricuspid valve disease. RHD contributed most to the burden of VHD in the present study with calcific degeneration, myxomatous disease and BAV being the other major forms of VHD. Multiple valves were affected in more than a third of all cases.

Burden and predictors of hypertension in India: results of SEEK (Screening and Early Evaluation of Kidney Disease) study

BackgroundHypertension (HTN) is one of the major causes of cardiovascular morbidity and mortality. The objective of the study was to investigate the burden and predictors of HTN in India.Methods6120 subjects participated in the Screening and Early Evaluation of Kidney disease (SEEK), a community-based screening program in 53 camps in 13 representative geographic locations in India. Of these, 5929 had recorded blood pressure (BP) measurements. Potential predictors of HTN were collected using a structured questionnaire for SEEK study.ResultsHTN was observed in 43.5% of our cohort. After adjusting for center variation (p < 0.0001), predictors of a higher prevalence of HTN were older age ≥40 years (p < 0.0001), BMI of ≥ 23 Kg/M2 (p < 0.0004), larger waist circumference (p < 0.0001), working in sedentary occupation (p < 0.0001), having diabetes mellitus (p < 0.0001), having proteinuria (p < 0.0016), and increased serum creatinine (p < 0.0001). High school/some college education (p = 0.0016), versus less than 9th grade education, was related with lower prevalence of HTN. Of note, proteinuria and CKD were observed in 19% and 23.5% of HTN subjects. About half (54%) of the hypertensive subjects were aware of their hypertension status.ConclusionsHTN was common in this cohort from India. Older age, BMI ≥ 23 Kg/M2, waist circumference, sedentary occupation, education less, diabetes mellitus, presence of proteinuria, and raised serum creatinine were significant predictors of hypertension. Our data suggest that HTN is a major public health problem in India with low awareness, and requires aggressive community-based screening and education to improve health.

Hydrogen Sulfide

Vascular calcification is the major cause of cardiovascular morbidity and mortality in patients with type 2 diabetes mellitus, chronic kidney disease, and in aging patients.1 Considerable progress has been made in the past 2 decades in understanding the molecular mechanisms of vascular calcification.2–4 Regardless of the morphology and location, most evidence indicates that vascular calcification involves an organized process recapitulating many cellular and molecular events that govern skeletal bone formation. Although a large body of evidence shows that osteoblastic and osteochonrocytic cells contribute to vascular calcification, it remains unclear how osteoclasts are differentiated from their precursors and how osteoclasts play a role in calcium reabsorption in calcifying arteries. Osteoclasts develop from monocytic precursors of the hematopoietic lineage, and 2 distinct signaling systems are both necessary and sufficient for the early differentiation into multinucleated osteoclasts as demonstrated by osteopetrotic mice models with loss-of-function mutation of either gene.5–7 One is a signaling system that involves macrophage colony-stimulating factor (MCSF) and its receptor c-fms, and the other involves receptor activator of nuclear factor κB (RANK) ligand (RANKL), RANK, and osteoprotegerin (OPG), a soluble decoy receptor for RANKL.8–10 MCSF and RANKL induce osteoclast differentiation, fusion, and maturation on binding to its specific receptors, c-fms and RANK, respectively, on the surface of preosteoclastic monocytes. Increased production of RANKL in atherosclerotic lesions, particularly in endothelial cells and vascular smooth muscle cells (SMCs), has been well documented.11–13 See accompanying article on page 626 Studies of …

Dietary Alpha-Linolenic Acid Does Not Protect From Venous Thrombosis In The Vena Cava Stenosis Model

BackgroundDeep vein thrombosis (DVT) and pulmonary embolism (PE) are major causes of cardiovascular morbidity and mortality. Omega-3 fatty acids (n-3 FA) are well known for their beneficial effects on primary and secondary prevention of cardiovascular disease (CVD). We and others have previously reported that n-3 FA, particularly the plant-derived alpha-linolenic acid (ALA), inhibits atherosclerosis, reduces arterial thrombosis and decreases platelet activation in mice fed an n-3-enriched diet by antiinflammatory, antiplatelet and anticoagulant mechanisms. In this study we investigated the effects of ALA on the development of DVT in the vena cava stenosis model in mice.HypothesisBecause platelet activation and inflammatory processes may play a relevant role in venous thromboembolism, we hypothesized that ALA prevents the development of venous thrombosis in mice undergoing vena cava stenosis due to its antiplatelet, anticoagulant and antiinflammatory properties. Methods12 to 14 weeks old C57/BL6 mice underwent 4 weeks of high- (7.3g%; hiALA) or low-ALA (0.03g%; loALA) treatment (n=11 per group) before they were exposed to vena cava stenosis. Rodents were anaesthetized, the inferior vena cava (IVC) was exposed and a ligature was placed proximal to the left renal vein in order to narrow the IVC and to provoke a reduction in blood flow and thereby induce thrombus formation. Mice were examined 48 hours after initial surgery; percentage of mice with thrombus formation and thrombus length were determined. Additionally, we performed blood count analysis and determined plasma glycocalicin index (ug/ml/250 000 platelets), the extramembranous portion of GPIbalpha, as a marker for platelet turnover and shedding of the platelet receptor for von Willebrand factor (vWF). ResultsContrary to our hypothesis, treatment with ALA did neither significantly reduce the incidence (hiALA, 55 % vs loALA, 64 %; n=11 per group, p=ns) nor size of venous thrombosis (hiALA, 2.4 mm vs loALA, 2.3 mm; n=11 per group, p=ns). Glycocalicin index was comparable in both groups (hiALA, 15.0±8.1 ug/ml/250 000 platelets vs loALA, 11.1±4.5 ug/ml/250 000 platelets; n=8 per group, p=ns), indicating no difference in platelet consumption. Interestingly, we observed an increased leukocyte count and a reduced platelet count in hiALA-treated mice after 48 hours of venous thrombosis, a difference that was not observed in sham operated mice. ConclusionsDietary ALA did not protect from DVT in the mouse model of vena cava stenosis chosen. Despite its protective properties in arterial thrombosis, ALA seems to be ineffective in the pathogenesis of the stenosis-induced venous thrombosis, possibly because the pathways of platelet activation and inflammation, modified by ALA, are of lower penetrance. The findings of increased leukocyte count and decreased platelet count after 48 h of VT warrant further investigation. Disclosures:No relevant conflicts of interest to declare.