Global Heart is the official and primary publication of the World Heart Federation, offering a platform for the dissemination of knowledge on research, developments, trends, solutions and public health programmes in the area of cardiovascular disease. Global Heart welcomes research results, points of view and educational material on the prevention, treatment and control of cardiovascular disease with a special focus on low and middle-income countries which are facing the brunt of epidemiological transition.Global Heart strongly encourages authors to adhere to CONSORT, STROBE, STARD, and PRISMA guidelines for reporting of clinical trials, observational studies, diagnostic test accuracy papers, and systematic reviews or meta-analyses. Authors are required for submission to download and complete the appropriate Equator Network checklist: http://www.equator-network.org/.
Hypertension is inadequately controlled in most patients due to poor adherence to treatment. Not much is known about the underlying reasons for poor adherence. The main objective of this study was to assess medication adherence in hypertensive patients and to identify the main barriers associated with medication adherence. A questionnaire-based survey was conducted in the medicine outpatient department of Kempe Gowda Institute of Medical Sciences and Research Centre, Bangalore, India. Self reported adherence was measured by using a short validated questionnaire and detailed patient interviews. Of the 608 patients participated, non-adherence was found in 49.67% of patients. Belief barrier was reported in 39.14% patients. Access barrier and recall barrier were reported by 82.57% and 62.17%, respectively. 78.62% of patients reported that it is difficult to pay for the medication and 54.93% indicated that it is difficult to get a refill on time. It was concluded that about half of the Indian patients studied were not adherent to their antihypertensive regimen and this might result in poor blood pressure control. Non-adherence to hypertension management remains a major limiting factor among Indians in the effective control of hypertension and in the prevention of cardiovascular diseases.
Global Heart is the official and primary publication of the World Heart Federation, offering a platform for the dissemination of knowledge on research, developments, trends, solutions and public health programmes in the area of cardiovascular disease. Global Heart welcomes research results, points of view and educational material on the prevention, treatment and control of cardiovascular disease with a special focus on low and middle-income countries which are facing the brunt of epidemiological transition.Global Heart strongly encourages authors to adhere to CONSORT, STROBE, STARD, and PRISMA guidelines for reporting of clinical trials, observational studies, diagnostic test accuracy papers, and systematic reviews or meta-analyses. Authors are required for submission to download and complete the appropriate Equator Network checklist: http://www.equator-network.org/.
Global Heart is the official and primary publication of the World Heart Federation, offering a platform for the dissemination of knowledge on research, developments, trends, solutions and public health programmes in the area of cardiovascular disease. Global Heart welcomes research results, points of view and educational material on the prevention, treatment and control of cardiovascular disease with a special focus on low and middle-income countries which are facing the brunt of epidemiological transition.Global Heart strongly encourages authors to adhere to CONSORT, STROBE, STARD, and PRISMA guidelines for reporting of clinical trials, observational studies, diagnostic test accuracy papers, and systematic reviews or meta-analyses. Authors are required for submission to download and complete the appropriate Equator Network checklist: http://www.equator-network.org/.
Global Heart is the official and primary publication of the World Heart Federation, offering a platform for the dissemination of knowledge on research, developments, trends, solutions and public health programmes in the area of cardiovascular disease. Global Heart welcomes research results, points of view and educational material on the prevention, treatment and control of cardiovascular disease with a special focus on low and middle-income countries which are facing the brunt of epidemiological transition.Global Heart strongly encourages authors to adhere to CONSORT, STROBE, STARD, and PRISMA guidelines for reporting of clinical trials, observational studies, diagnostic test accuracy papers, and systematic reviews or meta-analyses. Authors are required for submission to download and complete the appropriate Equator Network checklist: http://www.equator-network.org/.
We investigated the association of the variability of acute myocardial infarction (AMI) occurrences between warm and colder periods and the conventional cardiovascular risk-factors. For the registered 429 first-ever-AMI event, the odd of suffering an AMI during the colder period was significantly higher (OR 1.47, 95%CI: 1.21–1.78). None of the conventional cardiovascular risk factors explains the excess risk of AMI during the colder period pointing towards the influence of AMI triggering factors in the time preceding onset of AMI irrespective of presence or absence of cardiovascular risk-factors.
There are conflicting reports about the role of conventional risk factors in coronary artery disease from some of the studies in India. The present study tried to determine the association of conventional risk factors in patients with coronary artery disease (CAD) and correlate with findings on coronary angiography.
Global Heart is the official and primary publication of the World Heart Federation, offering a platform for the dissemination of knowledge on research, developments, trends, solutions and public health programmes in the area of cardiovascular disease. Global Heart welcomes research results, points of view and educational material on the prevention, treatment and control of cardiovascular disease with a special focus on low and middle-income countries which are facing the brunt of epidemiological transition.Global Heart strongly encourages authors to adhere to CONSORT, STROBE, STARD, and PRISMA guidelines for reporting of clinical trials, observational studies, diagnostic test accuracy papers, and systematic reviews or meta-analyses. Authors are required for submission to download and complete the appropriate Equator Network checklist: http://www.equator-network.org/.
Community Interventions for Health (CIH) is a 3year pilot study focusing on testing chronic disease prevention activities in developing country settings. CIH uses structural interventions and community mobilization, supported by health education and social marketing/media. The activities of CIH are pervasive throughout defined community settings using schools, work places, health care settings, and the community at large to create sustainable change. CIH seeks to: (1) assess the impact of the interventions on individuals and on the community, (2) assess the best methods for intervention implementation, (3) identify adaptations needed for global replication, and (4) identify community-specific barriers and facilitators to change. Additionally, the CIH study provides the larger medical and public health community with research and evaluation tools and methodology, including context assessment manuals, environmental scan tools and processes, and adaptations for developing country settings. CIH is building a large dataset of common measures across countries that may be used to inform local and national policies and practices. The purpose of this paper is to present the results of a several year planning process that includes a theoretical framework and study design that highlights the key elements of conducting complex community interventions in developing country settings.
OBJECTIVE:To describe the extent and content of tobacco-related images, advertising and articles published in the largest Argentinean newspapers before and after a voluntary advertising ban implemented in 2001.METHODS:Issues from four months of each year of the four main national newspapers were examined from 1995 to 2004. We recorded the number of tobacco images (advertisement or not), tobacco-focused articles, space used, and placement within the newspaper. Regression analyses evaluated time trends.RESULTS:We identified 1800 images and articles from 4828 different issues. Non-advertisement images were the most frequent (71.2%), followed by articles (20%) and advertisement images (8.8%). Advertisements only appeared in the two best selling newspapers with a majority (57%) in the Sunday magazine and 21% in the sports sections. Non-advertisement images were published in the sports and entertainment sections (55%) and showed a public figure in 88%. Of 336 articles, 39% focused on health topics and 55% emphasized the negative effects of tobacco on health. Regression models showed that prior to 2001 there were significant time-related decreases in ad images and articles and significant increases in non-ad images. The trend of each outcome changed direction beginning in 2001 and the magnitude of the change in trend was significant for ad images and non-ad images. The number of non-ad images dropped significantly in 2001 from a model-predicted value of 178 per year to 103 non-ad images and remained constant thereafter.CONCLUSIONS:Tobacco images exceeded information about tobacco hazards in Argentinean newspapers over this period. Advertisement increased from 2001 to 2005, following the voluntary advertisements ban. Partial advertisement bans are ineffective and a total ban is imperative.
Global Heart is the official and primary publication of the World Heart Federation, offering a platform for the dissemination of knowledge on research, developments, trends, solutions and public health programmes in the area of cardiovascular disease. Global Heart welcomes research results, points of view and educational material on the prevention, treatment and control of cardiovascular disease with a special focus on low and middle-income countries which are facing the brunt of epidemiological transition.Global Heart strongly encourages authors to adhere to CONSORT, STROBE, STARD, and PRISMA guidelines for reporting of clinical trials, observational studies, diagnostic test accuracy papers, and systematic reviews or meta-analyses. Authors are required for submission to download and complete the appropriate Equator Network checklist: http://www.equator-network.org/.
INTRODUCTION:The Malaysian National Cardiovascular Disease Database (NCVD) team presents Percutaneous Coronary Intervention (PCI) Registry report for the year 2007 to 2009. It provides comprehensive information regarding practice and outcome of PCI in Malaysia.METHODOLOGY:It was a voluntary, multi-centered, observational, cohort study and included patients of 18 years or above who underwent PCI at eleven participating centers in Malaysia from the year 2007 to 2009.RESULT:Ten thousand six hundred and two patients underwent 11,498 PCI procedures with 18,116 stents for 15,538 lesions. Mean age of the patients was 57 years and more than 98% of patients had at least one cardiovascular risk factor. A significant number of our patients were diabetic (50%) and had renal impairment (44.7% had ≤ stage 3 chronic kidney disease) at the time of procedure. Fifty eight percent of the lesions were type B2 or type C lesion. Twenty eight percent of the lesions had high risk characteristics. Procedural success rate was about 97% and post-procedural complications were low. Overall in-hospital, all cause mortality was 1%, of which 85% were cardiac related deaths. The poor prognostic factors for in-hospital mortality were acute coronary syndrome cases, higher Killip class and increasing age.CONCLUSION:Compared to other registries, Malaysian patients undergoing PCI were much younger with high prevalence of risk factors. In spite of complex and high risk lesions, procedural success was high, with overall low mortality rate. NCVD-PCI Registry aims to improve over-all cardiac services in Malaysia through its ongoing journey.
Coronary artery disease is one of the most rampant non-communicable diseases in the world. It begins indolently as a fatty streak in the lining of the artery that soon progresses to narrow the coronary arteries and impair myocardial perfusion. Often the atherosclerotic plaque ruptures and causes sudden thrombotic occlusion and acute ST-elevation myocardial infarction (STEMI), non-ST-elevation MI (NSTEMI) or unstable angina (UA). This phenomenon is called acute coronary syndrome (ACS) and is the leading cause of death not only in Malaysia but also globally. In order for us to tackle this threat to the health of our nation we must arm ourselves with reliable and accurate information to assess current burden of disease resources available and success of current strategies. The acute coronary syndrome (ACS) registry is the flagship of the National Cardiovascular Disease Database (NCVD) and is the result of the dedicated and untiring efforts of doctors and nurses in both public and private medical institutions and hospitals around the country, ably guided and supported by the National Heart Association, the National Heart Foundation, the Clinical Research Centre and the Ministry of Health of Malaysia. Analyses of data collected throughout 2006 from 3422 patients with ACS admitted to the 12 tertiary cardiac centres and general hospitals spanning nine states in Malaysia in this first report has already revealed surprising results. Mean age of patients was 59 years while the most consistent risk factor for STEMI was active smoking. Utilization of medications was high generally. Thirty-day mortality for STEMI was 11%, for NSTEMI 8% and UA 4%. Thrombolysis (for STEMI only) reduced in-hospital and 30-day mortality by nearly 50%. Percutaneous coronary intervention or PCI also reduced 30-day mortality for patients with non-ST elevation MI and unstable angina. The strongest determinants of mortality appears to be Killip Class and age of the patient. Fewer women received thrombolysis or underwent PCI on same admission although women make up 25% of the cohort.
Methods Patients with heart failure for up to 2 years, without a distinct cause, were enrolled in the Myocarditis Treatment Trial between 1986 and 1990. Frozen blood samples were available from 1315 to 2233 enrolled patients. Anti-cTnIAAB was determined by a two-step immunoassay. Results The mean (±SEM) value of serum Anti-cTnIAAB titer in the 1315 patients was 0.067 ± 0.003 arbitrary unit (AU), significantly higher than in 1115 healthy volunteers (0.053 ± 0.002 AU, P < 0.01). The mean Anti-cTnIAAB titer in 88 patients whose endomyocardial biopsies (EMB) satisfied the diagnostic Dallas criteria was 0.086 ± 0.010 AU, versus 0.066 ± 0.004 AU in 1227 patients whose EMB did not satisfy these criteria. The mean Anti-cTnIAAB in both groups was significantly higher than that measured in the healthy volunteers ( P < 0.01). The mean Anti-cTnIAAB titer in the 88 patients with Dallas criteria-confirmed myocarditis tended to be higher than in the other 1227 patients. Among the 88 patients with Dallas criteria-confirmed myocarditis, the mean Anti-cTnIAAB titer in 5 patients infected with the hepatitis C virus infection (HCV) was significantly higher (0.146 ± 0.047 AU) than in 83 patients without HCV infection (0.082 ± 0.010 AU, P < 0.05). Conclusions Elevated autoantibody titers against cTnI were detected in patients with myocarditis, and were higher in HCV-infected patients. The presence of Anti-cTnIAAB might correlate with inflammation and viral infection of the heart. Keywords Myocarditis Cardiac troponin I Autoantibody Hepatitis C virus Introduction There is much evidence to support the argument that some forms of human myocarditis and dilated cardiomyopathy (DCM) are the result of a pathogenic autoimmune response. The first line of evidence is the detection of heart-specific antibodies with demonstrated functional effects in a high proportion of patients suffering from these disorders. These antibodies may be present before the onset of DCM, and predict the evolution of disease from the perspective of myocardial function [1] . In addition, the depletion of heart-specific antibodies by extracorporeal immunoadsorption attenuates the disease manifestations in some patients, often for long periods of time [2] . Finally, clinical investigations have shown a benefit conferred by immunosuppression in a subpopulation of patients with DCM, while, in animals, autoimmune myocarditis was induced by viral infection, an autoimmune response that can be duplicated by immunization with cardiac myosin, a well-characterized antigen. This evidence suggests that some forms of DCM and myocarditis are caused by pathogenic autoimmune responses, representing the final common pathogenetic pathway of various infectious and non-infectious injuries [1] . In a recent study, we showed that mice lacking the T-cell receptor costimulatory molecule PD-1 spontaneously developed autoimmune DCM, along with the production of high autoantibody titers against cardiac troponin I (Anti-cTnI AAB) [3] , and that the passive transfer of monoclonal antibodies to cTnI induced myocardial dysfunction [4] . In this study, we developed a new Anti-cTnI AAB detection method, which we applied in a large population of patients with myocarditis and heart failure. Methods The design of the trial, methods of random treatment assignments, patient characteristics, and histopathologic techniques used to diagnose myocarditis have been described previously [5,6] . Briefly, consenting patients were eligible to enter the trial if they had (1) suffered from heart failure of undetermined etiology for up to 2 years, (2) a <45% left ventricular ejection fraction by radionuclide left ventriculography, (3) myocarditis proven by endomyocardial biopsy (EMB), and (4) no contraindications to immunosuppressive therapy. EMB was performed by standard techniques according to local institutional practices, and the specimens were fixed in formalin before being processed, sectioned, and stained with hematoxylin and eosin. The initial histopathologic diagnosis of myocarditis was made at each enrolling institution. The EMB samples were reviewed by a panel of seven expert pathologists, and the diagnosis of myocarditis verified on the basis of the Dallas criteria [7] . The Institutional Review Boards of each enrolling medical center reviewed and approved the study protocol, and all study participants granted their consent to the investigative use of all EMB materials and blood specimens. Among the 2233 patients enrolled in the trial, 111 who satisfied the Dallas criteria were ultimately randomly assigned to a treatment regimen. Frozen blood samples from 1314 enrollees were used for the investigations in this report. Cloning of human cardiac troponin I and expression of recombinant cardiac troponin I Human cardiac troponin I (cTnI) cDNA was obtained by reverse transcriptase–polymerase chain reaction (PCR) from total RNA of human heart (Clontech Laboratories Inc., Mountain View, CA). PCR was carried out using 5′-GACGGATCCATGGCCGATGGTAGCAGCGATGCGG-3′ as the sense primer and 5′-GACGAGCTCTCAGCTCTCAAACTTTTTCTTGCGG-3′ as the antisense primer for cTnI cDNA. The cTnI cDNA encoded amino acids 1–210 and was constructed with a 6xHis tag at the N-terminus. The cTnI cDNA was subcloned into the pQE-30 plasmid (Qiagen K.K., Tokyo, Japan) to yield the pQE-30/cTnI vector. Escherichia coli XL-blue (Toyobo, Tokyo, Japan) bearing the pQE-30/cTnI plasmid was cultured at 37 °C in Terrific Broth medium containing ampicillin at a concentration of 50 mg/l. The expression of recombinant cTnI was induced with 1 mM isopropyl thiogalactopyranoside, and the cells were harvested by centrifugation 5 h later. The cells were suspended in phosphate buffer (25 mM sodium phosphate and 0.5 M NaCl, at pH 8.0) and disrupted by sonication. The insoluble fraction was pelleted by centrifugation at 30,000 g for 30 min at 4 °C, and the pellet was dissolved in phosphate buffer at pH 8.0, which contained 6 M guanidine chloride, followed by sonication. The guanidine-soluble fraction was centrifuged at 30,000 g for 30 min at 4 °C, and the supernatant was loaded onto a nickel–nitrilotriacetic acid (Ni–NTA) agarose column (Qiagen). The recombinant protein was eluted with Tris buffer (20 mM Tris–HCl, pH 7.5) containing 7 M urea and 0.2 M imidazole, and the eluate was then applied onto a DEAE Sepharose column. The unbound fraction was loaded onto a CM Sepharose column and recombinant cTnI protein was eluted with a linear gradient of 0–0.5 M NaCl. The partial length of cTnI cDNA (middle-cTnI), corresponding to amino acids 41–110 of cTnI, was obtained by PCR using: 5′-GACGGATCCATCTCCGCCTCGAGAAAATTGCAGC-3′ as the sense primer and 5′-GACGAATTCTCAGTGATGGTGATGGTGATGCTCTTCATCCACCTTGTCCACACGG-3′ as the antisense primer for middle-cTnI cDNA. The middle-cTnI cDNA was constructed with a 6xHis tag at the C-terminus and subcloned into the pGEX-2T plasmid (Qiagen) to yield the pGEX-2T/middle-cTnI vectors. E. coli JM-109 (Toyobo) bearing the pGEX-2T/middle-cTnI plasmid was cultured and expression was induced in TB medium as described earlier. The purity of purified recombinant c-TnI and middle-cTnI, subjected to SDS–PAGE and visualized by Coomassie brilliant blue staining, was ascertained by gel scanning, using the Intelligent Quantifier system (Bio Image Systems Inc., Jackson, MI), as described previously [8] . Identification of autoantibody against cardiac troponin I The anti-cTnI autoantibody (Anti-cTnIAAB) was identified by a two-step immunoassay. In a first step, recombinant cTnI (0.5 μg/well) was first coated in a microtiter plate (Nunc™ Immuno Plate II) by overnight incubation at 4 °C. The wells were then blocked for 2 h with 200 μl of phosphate buffer solution (PBS) containing 30 g/l of bovine serum albumin (BSA), at room temperature. After washing of the plate with 200 μl of PBS containing 1 g/l of Tween 20, 100 μl serum samples (1:10) diluted with PBS containing 1 g/l of Tween 20 were added and incubated overnight at 4 °C. After the plate had been washed five times, 100 μl of glycine buffer (10 mM glycine–HCl at pH 2.7) was added to each well, and 50 μl from each well was transferred and mixed with 50 μl of PBS at pH 8.0, containing 0.2% BSA and 0.2% Tween 20 in the well of another plate (IgGs solution). In a second step, recombinant middle-cTnI (0.5 μg/well) was coated in a microtiter plate by overnight incubation at 4 °C. The wells were then blocked for 2 h, at room temperature, with 200 μl of PBS containing 30 g/l of BSA. After washing of the plate with 200 μl of PBS containing 1 g/l Tween 20, 100 μl of IgGs solution was added and incubated for 2 h at room temperature. After the plate had been washed five times, 100 μl of horseradish peroxidase-labeled sheep anti-human IgG antibody (1:20,000) was added to each well and incubated for 1 h at room temperature. After the plate was washed, 100 μl of substrate solution (50 mM citrate–phosphate buffer at pH 5.0) containing 0.4 g/l o-phenylenediamine dihydrochloride and 0.15 ml/l H 2 O 2 were added to each well. The reaction was stopped after 30 min by the addition of 50 μl of 4 mol/l H 2 SO 4 . The absorbance was measured at 492 nm with a microplate reader. Serum Anti-cTnIAAB titers are expressed as arbitrary units (AU) [8] . Statistical analysis Between-groups differences were examined by Student’s t- test. Other comparisons were made by one-way analysis of variance, with multiple comparisons tested by Fisher’s least significant difference. All values are presented as means ± standard error of the mean (SEM). Differences were considered statistically significant when P was <0.05. Results The mean (±SEM) titer of serum Anti-cTnIAAB (0.067 ± 0.003 AU) measured in the 1315 patients enrolled in the Myocarditis Treatment Trial was significantly higher than that measured in 1115 healthy volunteers (0.053 ± 0.002 AU, P < 0.01; Fig. 1 ). The mean titer of Anti-cTnIAAB in 88 patients whose EMB satisfied the Dallas criteria was 0.086 ± 0.010 AU, versus 0.066 ± 0.004 AU in 1227 patients whose EMB did not satisfy the Dallas criteria. Both values were significantly higher than that measured in healthy volunteers ( P < 0.01; Fig. 2 ). The elevated levels of anti-troponin I antibody observed in patients whose EMB satisfied the Dallas criteria tended to be higher than those measured in patients whose EMB did not satisfy the Dallas criteria, though the difference did not reach statistical significance ( Fig. 2 ). Among 88 patients whose EMB satisfied the Dallas criteria, five were infected with the hepatitis C virus (HCV). These five patients had significantly higher Anti-cTnIAAB titers (0.146 ± 0.047) than the 83 patients not infected with the HCV and whose EMB satisfied the Dallas criteria (0.082 ± 0.010, P < 0.05; Fig. 3 ). However, there was no significant difference in Anti-cTnIAAB titers between patients with versus without HCV infection whose EMB did not satisfy the Dallas criteria ( Fig. 4 ). Discussion Anti-cardiac antibodies have been observed in patients with myocarditis and DCM [9,10] . Several immunofluorescent patterns have been described, including fibrillary, sarcolemmal, cytoplasmic and others. The presence of anti-fibrillary antibodies suggests that cardiac myofibrils might be a prominent antigen in myocarditis [10] . An antibody to cardiac myosin has often been observed in patients with DCM [11] , and alpha and beta myosin heavy chain isoforms both react with that autoantibody [12,13] . Antibodies to the mitochondrial ADP/ATP translocator or β 1 -adrenoceptor, often present in patients with DCM, enhance the Ca 2+ current [14–16] . We have shown that dihydropyridine-insensitive Ca 2+ -permeable cation channels, but not voltage-gated Ca 2+ channels, are activated by anti-cardiac antibodies associated with myocarditis in ventricular myocytes. It is likely that the excess Ca 2+ entry, caused by the activation of this new channel by disease-associated antibodies, is involved in the pathogenesis of myocarditis and DCM [17] . We have recently discovered that mice lacking the T-cell receptor costimulatory molecule PD-1 spontaneously develop autoimmune DCM, along with the production of high titers of antibodies to cTnI. The passive transfer of monoclonal antibodies to cTnI induces myocardial dysfunction in mice [4] . Our experimental observations support the hypothesis of an interaction between cTnI-specific antibodies and cTnI on the surface of cardiomyocytes, enhancing the Ca 2+ current and, eventually, causing cardiac dysfunction and dilation. However, we cannot exclude the possibility that antibodies to cTnI penetrate the plasma membrane and recognize cTnI in sarcomeres. Our study provided the first direct evidence of an implication of autoimmunity, autoantibodies in particular, in the development of DCM in an animal model. In the present study, we developed a new method to detect autoantibodies against cTnI, and we measured these autoantibodies in patients with myocarditis. Myocarditis, defined by the Dallas criteria as “the presence of an inflammatory infiltrate in the myocardium with necrosis and/or degeneration of adjacent myocytes” remains an etiologic dilemma and a therapeutic challenge [7] . Different microorganisms can cause the same pathologic manifestations, although they mandate different therapies [18] . Several microorganisms have been identified as possible pathogens, including enteroviruses, adenoviruses and HCV [19–23] . We detected higher Anti-cTnIAAB titers in patients with myocarditis whose EMB satisfied the Dallas criteria than in those whose EMB was negative. Furthermore, among those whose EMB satisfied the Dallas criteria, those in whom an anti-HCV antibody was detected had higher titers than those who were not infected with the HCV. Our study showed that Anti-cTnIAAB is often present in patients with active myocarditis, suggesting that their presence correlates with ongoing inflammation. In our previous studies, we found that HCV infection is often associated with myocarditis [20–23] , and that myocardial injury is particularly severe in patients infected with the HCV. In this study, the Anti-cTnIAAB titers were higher in patients with, than patients without, HCV infection. One might hypothesize that infection with the HCV increases the production of Anti-cTnIAAB and further increases the severity of myocardial injury. Therefore, the detection of Anti-cTnIAAB might be helpful in the diagnosis, as well as the evaluation and follow-up, of patients presenting with active myocarditis. Chronic heart failure patients have been reported to have elevated circulating concentrations of bacterial endotoxin with significant activation of immune cells [24,25] , and it is known that bacterial endotoxin stimulates many immunocompetent cells including B lymphocytes [26] . We have recently demonstrated that leukocytes, especially macrophages are the major target of HCV infection [23] . It has been shown that HCV infection can enhance expression of toll-like receptors (TLRs) that are critical to promote innate immune responses [27] . Thus, HCV infection may activate B lymphocytes through up-regulations of TLRs, and increase Anti-cTnIAAB. In experimental studies, Anti-cTnIAAB was detected from the subacute to chronic stage after infection with coxsackie virus B3 in mice [28] . Immunization with recombinant murine cTnI caused severe inflammation of the myocardium with increased expression of inflammatory chemokines, and the inflammation was followed by cardiomegaly, fibrosis, reduced fractional shortening, and significant mortality. In contrast, mice immunized with murine cardiac troponin T showed little or no inflammation and no death [29] . Furthermore, troponin I-specific T cells induced inflammation and fibrosis in mice [30] . Recently, Anti-cTnIAAB has been shown in normal blood donors [31] , and absence of Anti-cTnIAAB was associated with improvement of left ventricular function after acute myocardial infarction [32] . Recent observations suggest that immunoadsorption with a view to removing circulating autoantibodies confers therapeutic benefits [33] . In these clinical experiments, patients with idiopathic DCM underwent extracorporeal adsorption of immunoglobulin by an anti-IgG column. It was further observed that immunosuppression in patients with active myocarditis was most likely to improve cardiac function when circulating cardiac autoantibodies were present [30] . Additional studies might show a benefit conferred by the immunoadsorption of Anti-cTnIAAB, or by immunosuppression to inhibit their production, in patients in whom these antibodies are detected. Measurement of Anti-cTnIAAB is a simple and specific tool to detect inflammation in the heart, and is suitable for population-based study. Modulation of the production of Anti-cTnIAAB may prevent the development of myocarditis, and could be a cost-effective approach to address this increasing disease entity. Acknowledgment This work was supported, in part, by a research grant from the Japanese Ministry of Health, Labor and Welfare , and a grant for scientific research from the Japanese Ministry of Education, Culture, Sports, Science, and Technology . We thank Ms. M. Hayashi for preparing the manuscript. References [1] N.R. Rose The significance of autoimmunity in myocarditis H.-P. Schultheiss J.-F. Kappa G. Grötzbach Chronic viral and inflammatory cardiomyopathy 2006 Springer-Varlag Berlin 141 145 [2] S.B. Felix A. Staudt G.B. Friedrich Improvement of cardiac function after immunoadsorption in patients with dilated cardiomyopathy Autoimmunity 34 2001 211 215 [3] H. Nishimura T. Okazaki Y. Tanaka K. Nakatani M. Hara A. Matsumori Autoimmune dilated cardiomyopathy in PD-1 receptor deficient mice Science 291 2001 319 322 [4] T. Okazaki Y. Tanaka R. Nishio T. Mitsuiye A. Mizoguchi J. 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Material and methods In this cross sectional study, 10,000 patients with CVD were recruited. This 1 year study was conducted in the outpatient department of Armed Forces Institute of Cardiology/National Institute of Heart Diseases (AFIC-NIHD), which provides primary, secondary and tertiary cardiac care to patients from all over the country. The CVD risk factors studied included hypertension, diabetes, dyslipidemia, obesity, smoking, alcohol intake, inactivity, eating <5 portions of fruits and/or vegetables per day. Results and discussion Of the study participants 73.5% were males while 26.5% were females. Their average age was 53.83 ± 14.18 years and 51.68 ± 15.83 years, respectively. The frequency of premature CVD was 27.2% in males and 49.1% in females. 46.9% males and 77.4% females had abdominal obesity, 15.6% men and 1.9% women being current smokers. Blood cholesterol levels were >200 mg/dl in 10% of all study subjects. In a decreasing order, poor lipid values were seen for HDL, VLDL, TG, cholesterol, LDL and LDL/HDL. Diabetes and hypertension affected 18.5% and 8% study subjects, respectively. Mean BMI was 21.02 kg/m 2 in men and 22.41 kg/m 2 in women. 64.5% participants did not take five or more servings of fruits and/or vegetables per day. 66% males and 68% females were physically inactive. Conclusion Risk factors in Pakistani patients can be rank ordered as abdominal obesity, eating <5 portions of fruits and/or vegetables per day, HDL, physical inactivity, diabetes, VLDL, TG, smoking, cholesterol, hypertension, obesity, LDL, LDL/HDL and alcohol. Keywords CVD Risk factors Pakistanis South-Asians Introduction The term cardiovascular disease (CVD) includes coronary heart disease (CHD), stroke, heart failure, hypertension, peripheral arterial diseases, congenital causes and rheumatic heart disease (RHD) [1] . CVD is the leading cause of morbidity and mortality all over the world [2,3] , with the exception of Sub Saharan Africa [4] . Globally, CVD caused 17.1 million deaths in 2004, as per World Health Organization (WHO) estimates [5] . Eastern Mediterranean Region (EMR) countries [6] , which include Pakistan, are plagued with the double burden of disease. South-Asia bears an outsized share of the global burden of CVD. Pakistan is among the worst-hit countries [7] . Multiple factors have been incriminated for CVD aetiology. These risk factors play an important role in a person’s chances of developing the disease. The common modifiable risk factors include unhealthy diet, physical inactivity and tobacco smoke; while others are nonmodifiable, like age, male gender and heredity. Still others are termed as intermediate risk factors like hypertension, diabetes, abnormal blood lipids, and overweight/obesity [8] . Psycho-social stress, socio-economic status (SES), and history of taking contraceptive pills [9] are other known risk factors. Some novel risk factors [10] are being increasingly considered for their contribution to CVD. The CVD risk factor profile of South-Asians from Pakistan, India, Nepal, Bangladesh and Sri Lanka etc. is different from that of other ethnic groups. There are variations within the different Asian groups themselves and also between the various countries [11] . Publication have extensively elucidated the phenomenon “South-Asian paradox”. South Asians have a greater susceptibility to CVD due to an increased risk of atherosclerosis and are affected at a relatively younger age, despite low risk factor density. Their disease is more severe, extensive and associated with adverse outcomes, as compared to their European, American, and other Asian counterparts. Unfortunately, few individuals can be labelled as having ideal cardiovascular health [11] . We carried out the study with the objective of compiling a risk factor profile of Pakistani patients suffering from CVD. Our work on the subject has significance as we have attempted to study CVD in a Pakistani context, which is important. Management of CVD imposes a substantial financial burden on health care payers and Pakistan is a developing, resource-constrained country. It is located in South Asia, a region badly affected by the CVD epidemic and its resultant high mortality. Moreover, it is an EMR country, a region grappling with the double burden of disease. Furthermore, it is one of the most populous countries of the world, a fact that increases the vulnerabilities manifold. Material and methods This cross sectional study was conducted at Armed Forces Institute of Cardiology/National Institute of Heart Diseases (AFIC-NIHD), located in Rawalpindi, Pakistan, which provides primary, secondary and tertiary cardiac care not only to military personnel but also civilian population. Our military beneficiaries comprise of serving and retired (army, navy and air force) officers and soldiers and their entitled family members. Our civilian clientele includes employees and the entitled family members of Federal government and panel organizations along with the civilians paid out of the defence budget, civilians paying out-of-pocket and the poor and needy, whose treatment charges are borne by Zakat and Bait-ul-maal (social welfare funds). The study was carried out from March 2009 to March 2010, after obtaining necessary approval from the institutional review board. The study subjects were a cohort of self reporting, doctor diagnosed patients with CVD, reporting to the out-patients department of AFIC-NIHD, in the course of their routine medical check-up. Those who were >20 years of age and gave their voluntary, informed consent for participation, were included in the study through consecutive sampling. The exclusion criteria were any acute cardiac event warranting treatment forthwith, known advanced stage of any form of cancer, liver disease, kidney failure, psychiatric ailment, dementia, mental retardation and pregnancy. The study instrument was a detailed interviewer-administered questionnaire, in which the respondents were asked to comment on their demographic attributes, family history and CVD risk profile. After an overnight fast of 12 h, blood samples were drawn by trained nursing assistants. A central laboratory analyzed the specimens for fasting plasma glucose and lipid profile. The reports were handed over to patients within a few hours, who subsequently proceeded to the out-patients department. In the waiting area, all information from patients was gathered by a team of trained, junior medical officers, who endorsed results of the patients’ laboratory findings and also assessed their BP, height, weight, WC and calculated their BMI. All socio-demographic variables were operationally defined. Educational level was defined as under or above matriculation depending upon completing/not completing 10 years of formal schooling. Based on their area of birth, Pakistani nationals were sub-classified as belonging to Punjab, Sindh, NWFP, Balochistan and Kashmir. Place of residence was further divided into urban and rural. Urban areas were defined as cities and towns having a population of >100,000 people. Income was defined as money received on a monthly basis from all sources. Income was divided in classes as: Rs. <10,000, 10,000–25,000 and >25,000. In the family history, the presence of hypertension, diabetes, obesity and hypercholesterolemia in a parent, siblings and first degree relatives was questioned. The definition of smoking only pertained to cigarettes and was based upon the individuals’ self reporting. Subjects were divided into three categories of current, former (left smoking 1 year ago) and never smokers. Abnormal lipids were defined as all lipid values, above the normal/reference range or a history of taking lipid lowering drugs. These reference ranges were: cholesterol < 200 mg/dl, triglyceride (TG) < 200 mg/dl, low density lipoprotein (LDL) < 150 mg/dl, very low density lipoprotein (VLDL) < 38 mg/dl, high density lipoprotein (HDL) < 38 mg/dl and HDL/LDL ratio <4. Diabetes was defined as a fasting plasma glucose level ⩾ 126 mg/dl. Hypertension was defined as systolic blood pressure (BP) ⩾ 140 mm Hg and/or diastolic BP ⩾ 90 mm Hg measured 20 min apart, on two separate occasions. Obesity was defined as body mass index (BMI) ⩾ 30.0 kg/m 2 and BMI in turn was calculated as height in kg/m 2 . Central obesity was defined as waist circumference (WC) in men ⩾ 88 cm; and in women ⩾ 80 cm and WC was measured mid way between the last rib and the iliac crest with an inch-tape. The study subjects were also asked about their daily consumption of fruits and/or vegetables. Eating <5 portions per day was considered a risk factor. Physical inactivity was a dichotomous variable, which was defined as the lack of physical activity. Physical activity was defined as doing vigorous exercise for 20 min or more three or more times per week. It was gauged subjectively by asking the participants about their leisure time activity. Alcohol users were categorized as current, former and never users. All submitted questionnaires having missing data values for any variable were not included in the study. Data was analyzed using SPSS version 15. For quantitative variables, mean and standard deviation (SD) and for qualitative variables, frequencies along with percentage were used for description of variables. Independent sample’s t -test was used for comparison of quantitative variables while chi-square test was used for comparison of qualitative variables between different groups. A two-tailed p < 0.05 was considered statistically significant. Results The study spanned a period of 1 year during which a total of 10,000 patients with CVD were recruited. All were Pakistani nationals. The details of their socio demographic profile are depicted in ( Table 1 ). 7350 were males and 2650 were females. Average age for men and women was 53.83 ± 14.18 years and 51.68 ± 15.83 years, respectively. The age group most affected by CVD, in males was 50–59 years and in females was 60–69 years. The frequency of premature CVD (onset of CVD before the age of 45 years in men and 55 years in women) was 27.2% in males and 49.1% in females. Risk factors clustered in the 45–65 years age bracket ( Fig. 1 ). Among those recruited, 42.2% males and 75.5% females were under-matriculation. The difference in education level between genders was highly significant. As regards marital status 95.9% males and 73.6% females were married. The difference between genders for marital status is also highly significant. As regards area of residence, 58.5% participants belonged to rural areas. Highly significant difference were seen between genders for areas of residence and also between genders for socio-economic status. The values for all the risk factors studied are summarized in ( Tables 2 and 3 ). Smoking was found to be a major risk factor in men. Of the men and women 15.6% and 1.9% were current smokers, respectively. A significant association was observed between smoking and gender. Average cholesterol levels in men and women were found to be 149.66 and 150.49 mg/dl, respectively. Blood cholesterol levels were in excess of 200 mg/dl in 10% of all study subjects, the rates being 9.5% in men and 11.3% in women. In a decreasing order bad lipids were depicted by HDL, VLDL, TG, Cholesterol, LDL/HDL and LDL. The frequency of diabetes mellitus was 18.5% in all study subjects. Hypertension was detected in 8% of the adult population. For obesity, BMI was calculated. Mean BMI was found to be 21.02 kg/m 2 in men and 22.41 kg/m 2 in women. Of all the study subjects, 5.5% were labelled as obese, 4.1% of men and 9.4% women. For central obesity WC was calculated. On this basis 55% of the patients were obese. Participants were asked about their intake of five or more servings of fruits and/or vegetables per day, to which 64.5% replied in the negative. Almost the same level of physical activity was observed in both males and females though males were found to be slightly more active than females. Alcohol users were very few among the study subjects i.e. 2.5%. The frequency in males and females was 2.7% and 1.9%, respectively. Discussion This study was conducted to determine the risk factor profile of Pakistani patients. Our study cohort comprised of 10,000 CVD patients, all Pakistani nationals by birth. All the four provinces and Kashmir as well as the urban and rural areas of the country were adequately represented. The mean age of study participants and the frequency of premature CVD indicate that women are affected earlier. These statistically significant differences have implications in terms of healthcare costs. Various studies from Bangladesh, India and Sri lanka [12–14] have confirmed these findings. 95.9% males and 73.6% females were married. The difference in marital status between the genders was highly significant. As a proxy measure, it showed that women tend to live longer and hence after spousal death, suffered social isolation. Others [15] have also confirmed that married individuals are at a reduced risk of CVD morbidity and mortality. Sederholm et al. [16] have highlighted the gender differential and concluded that women have a higher risk factor burden than their male counterparts. The largest gender difference was seen for hypertension and diabetes, with a 50% higher rate in women as compared to men. In our study the largest gender difference was seen in abdominal obesity which was 77.4% in females and 46.9% in males.( p < 0.001). We studied the risk factors hypertension, diabetes, dyslipidemia, abdominal obesity, smoking, alcohol intake, inactivity, eating <5 portions of fruits and/or vegetables per day. Together they accounted for 92.5% of our CVD burden. Only for 7.5% patients, no risk factor could be incriminated. According to Grau et al. [17] , hypertension, diabetes, dyslipidemia, obesity and smoking explain 97% of the CVD burden. In order of decreasing frequency, risk factors in Pakistani males were physical inactivity, decreased consumption of fruits and or vegetables, abdominal obesity, HDL, diabetes, VLDL, TG, smoking, cholesterol, hypertension, LDL/HDL, obesity, LDL and alcohol. In Pakistani females they were abdominal obesity, decreased consumption of fruits and or vegetables, physical inactivity, HDL, VLDL, diabetes, TG, hypertension, cholesterol, obesity, LDL, LDL/HDL, smoking and alcohol. We found a single risk factor in 25.5% of CVD patients, two in 31.5%, three in 27.5%, four in 6.5 of the patients. None of the patients presented with 5, 6, 7 or 8 risk factors. Iqbal [18] has studied the proportions of three risk factors occurring singly, doubly and all three together and has discovered the respective frequencies to be 39%, 11% and 1%. Khot [19] found that only 10–15% of patients lacked any of the four conventional risk factors (smoking, diabetes, hyperlipidemia and hypertension) and 1 of the 4 risk factors was present in 84.6% of women and 80.6% of men. Males were found to be more active than females. Similar results have been reported by other researchers [20,21] . Our results are similar to Gupta’s [22] for female smoking but differ markedly from others [23] . Our study showed a smoking frequency of 15.6% in men and 1.9% in women which is similar to Motlagh’s [24] estimates. We differ from those of a Karachi based study [25] which found the frequency to be 21–33%. Our study colludes with other studies [21,22] in similarity of diabetes frequency in men and women. The estimates for obesity (as per BMI) vary markedly in various studies. Our noted frequencies of 4.1% in men and 9.4% in women, are strikingly different from those of Gupta’s [22] figures of 54.5% and 61.3%, respectively. In Middle East [24] the frequency was 24.5% and women were found to be affected, more commonly. Jafar’s [21] , results are similar. Nanan [26] , has reported the frequency of obesity as 23% and 40% in 45–64 year old Pakistani men and women, respectively. The prevalence of abdominal obesity as per our study was 46.9% in men and 77.4% in women. Gupta [22] noted it to be 61.0% and 54.30%; respectively. For hypertension, our findings are very different from those of Gupta [22] but somewhat closer in frequency, to a Middle Eastern [23] estimate of 21.7%. Our results are in agreement with others [21] with hypertension occurring more commonly in women. Generally, women [27] have more dyslipidemia. Higher levels of HDL-C, are found in Latin America, while lower levels are found in England and China [28] . Our HDL-C findings are similar to those of some researchers [22] . Our average cholesterol levels in men and women were 149.66 and 150.49 mg/dl, respectively and affected 9.5% men and 11.3% women. They are markedly different from Gupta’s findings (32.6% men and 39.5% women). Higher triglycerides values were found in 16.3% men and 17% women which match some other research results [29] but differ from Gupta’s [22] (42.9% in men and 43.4% in women). Only 36.7% men and 32.1% women consumed fresh fruits and vegetables. A study from Karachi [30] revealed higher frequencies. Limitations of the study Some limitations of our study should be noted. Although we are confident that our observations are an accurate representation of Pakistani patients; caution must be exercised when our conclusions are extrapolated to apply to healthy Pakistanis or those in other parts of the world. This was a facility-based study, confined to adult CVD patients and our data pertained to a single-centre. Among all known risk factors, we could not account for especially psycho-social stress; however, we identified and studied the major ones. Moreover, estimation of variables such as consumption of <5 portions of fruits and/or vegetables per day, physical inactivity, alcohol and smoking was based solely on patients’ self-reports. Recall bias may have distorted some of our results. Data were collected by especially trained medical officers; still there were missing values in 1.3% of questionnaires. As is true for all cross-sectional studies, the study design did not provide direct evidence of incidence, outcome and inference of causality or allow assessment of change. These deficiencies can be best addressed in subsequent, adequately powered studies. Strengths of the study The study sample was large, nationally representative and had no urban bias. This fairly allows for a generalization of our results. Traditional CVD risk factors namely diabetes, hypertension, obesity and dyslipidemia were objectively measured after the initial patients’ accounts. This makes our findings valid and reproducible for Pakistanis residing within their native country. All blood specimens were analyzed by a central laboratory. Observer bias was overcome by imparting extensive training to the data collectors. Potential implications This study has potential implications, at multiple levels. Locally, an in-depth knowledge of the risk factor profile of our patients will help us improve our functions as an institute. Evidence-based operation of individual risk factor clinics, cardiac rehabilitation programs, exploration of newer research avenues, meaningful health promotion and disease prevention endeavors will translate into effective and efficient health service organization and delivery. Nationally, a chronic disease policy can be formulated and adopted. Exercising allocative efficiency will strengthen the case for CVD preventive interventions, like provision of enabling environments for physical activity to all, at the community level as well as in the high risk groups. Internationally, it will act as a stable research base for detecting gender and ethnic differences in the prevalence of CVD. Acknowledgements Authors would like to extend a heartiest gratitude to Drs. Syed Shahid Nafees Zaidi, Saima Zahir, Saba Shaukat, Zilfah Younis, Fauzia Aslam, Mehwish Ara Shams, Nadia Tayyub, Amna Naveed, Shazia Malik, Huma Rashid, Raja Adnan Arif and Samiya Razzaq . References [1] M.J. Lamonte Epidemiology of cardiovascular disease J.L. Durstine G.E. Moore M.J. Lamonte B.A. Franklin Pollock’s textbook of cardiovascular disease and rehabilitation 2008 Human kinetics USA 9 16 [2] G.D. Backer Prevention of cardiovascular disease in asymptomatic people Heart 96 2010 477 482 [3] J.S. Berger C.O. Jordan D. Lloyd-Jones R.S. Blumenthal Screening for cardiovascular risk in asymptomatic patients J Coll Cardiol 55 2010 1169 1177 [4] T.A. Gaziano Reducing the growing burden of cardiovascular disease in the developing world Health Affairs 26 1 2007 13 24 [5] K. Lock J. Pomerlau L. Causer D.R. Altman M. 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Chronic hepatitis C virus infection has been associated with several extrahepatic manifestations, among these, renal and cardiac involvement. However, morphological evidence of hepatitis C virus localization in various organs remains to be clarified.
Four hundred and 16 subjects (average age, 56.2years; range, 20–92years; Men/Women, 207/209) undergoing annual health check-up were studied for the effect of aging and hypertension on arterial compliance or elasticity index, which were measured after a 10min rest in the supine position using CR-2000. Thirteen additional elderly patients with hypertension were also studied at rest in the supine position 30min before and after 8mg benidipine oral administration at the beginning of treatment and then repeatedly studied after a 10min rest over at least 4–7weeks to examine the effect of benidipine hydrochloride 8mg on arterial compliance in a similar manner. Systolic blood pressure and pulse pressure were increased in subjects above 40years of age. Diastolic blood pressure was also increased up to 60years of age but after 60years of age, it was decreased or rather it plateaued. Above 40years of age, large and small arterial compliance levels were significantly decreased with advancing age. Small arterial compliance was much more decreased than large arterial compliance. In hypertensive subjects, small and large arterial compliance levels were significantly decreased in comparison with normotensive subjects. Benidipine hydrochloride 8mg was given orally every morning in elderly hypertensive patients for at least 1month, and blood pressure and arterial compliance were measured every week using CR-2000. Benidipine hydrochloride decreased blood pressure and improved arterial compliance gradually and safely without any adverse effect. Therefore, benidipine hydrochloride is thought to be a useful antihypertensive drug for elderly hypertensives because of its potential to improve arterial function and perhaps arterial properties.
Global Heart is the official and primary publication of the World Heart Federation, offering a platform for the dissemination of knowledge on research, developments, trends, solutions and public health programmes in the area of cardiovascular disease. Global Heart welcomes research results, points of view and educational material on the prevention, treatment and control of cardiovascular disease with a special focus on low and middle-income countries which are facing the brunt of epidemiological transition.Global Heart strongly encourages authors to adhere to CONSORT, STROBE, STARD, and PRISMA guidelines for reporting of clinical trials, observational studies, diagnostic test accuracy papers, and systematic reviews or meta-analyses. Authors are required for submission to download and complete the appropriate Equator Network checklist: http://www.equator-network.org/.
During the last couple of years, the focus of attention has drifted from coronary risk to cardio-metabolic risk because of the growing epidemic of cardio-metabolic disorders such as obesity, metabolic syndrome, diabetes, and cardiovascular disease (CVD). Physical inactivity and consumption of high-energy foods are the root causes of this epidemic.
