Genetic determinants of major blood lipids in Pakistanis compared with Europeans.

BACKGROUND: Evidence is sparse about the genetic determinants of major lipids in Pakistanis. METHODS AND RESULTS: Variants (n=45 000) across 2000 genes were assessed in 3200 Pakistanis and compared with 2450 Germans using the same gene array and similar lipid assays. We also did a meta-analysis of selected lipid-related variants in Europeans. Pakistani genetic architecture was distinct from that of several ethnic groups represented in international reference samples. Forty-one variants at 14 loci were significantly associated with levels of HDL-C, triglyceride, or LDL-C. The most significant lipid-related variants identified among Pakistanis corresponded to genes previously shown to be relevant to Europeans, such as CETP associated with HDL-C levels (rs711752; P<10(-13)), APOA5/ZNF259 (rs651821; P<10(-13)) and GCKR (rs1260326; P<10(-13)) with triglyceride levels; and CELSR2 variants with LDL-C levels (rs646776; P<10(-9)). For Pakistanis, these 41 variants explained 6.2%, 7.1%, and 0.9% of the variation in HDL-C, triglyceride, and LDL-C, respectively. Compared with Europeans, the allele frequency of rs662799 in APOA5 among Pakistanis was higher and its impact on triglyceride concentration was greater (P-value for difference <10(-4)). CONCLUSIONS: Several lipid-related genetic variants are common to Pakistanis and Europeans, though they explain only a modest proportion of population variation in lipid concentration. Allelic frequencies and effect sizes of lipid-related variants can differ between Pakistanis and Europeans.

Association of the 9p21.3 locus with risk of first-ever myocardial infarction in Pakistanis: case-control study in South Asia and updated meta-analysis of Europeans.

OBJECTIVE: To examine variants at the 9p21 locus in a case-control study of acute myocardial infarction (MI) in Pakistanis and to perform an updated meta-analysis of published studies in people of European ancestry. METHODS AND RESULTS: A total of 1851 patients with first-ever confirmed MI and 1903 controls were genotyped for 89 tagging single-nucleotide polymorphisms at locus 9p21, including the lead variant (rs1333049) identified by the Wellcome Trust Case Control Consortium. Minor allele frequencies and extent of linkage disequilibrium observed in Pakistanis were broadly similar to those seen in Europeans. In the Pakistani study, 6 variants were associated with MI (P<10(-2)) in the initial sample set, and in an additional 741 cases and 674 controls in whom further genotyping was performed for these variants. For Pakistanis, the odds ratio for MI was 1.13 (95% CI, 1.05 to 1.22; P=2 x 10(-3)) for each copy of the C allele at rs1333049. In comparison, a meta-analysis of studies in Europeans yielded an odds ratio of 1.31 (95% CI, 1.26 to 1.37) for the same variant (P=1 x 10(-3) for heterogeneity). Meta-analyses of 23 variants, in up to 38,250 cases and 84,820 controls generally yielded higher values in Europeans than in Pakistanis. CONCLUSIONS: To our knowledge, this study provides the first demonstration that variants at the 9p21 locus are significantly associated with MI risk in Pakistanis. However, association signals at this locus were weaker in Pakistanis than those in European studies.

The Pakistan Risk of Myocardial Infarction Study: a resource for the study of genetic, lifestyle and other determinants of myocardial infarction in South Asia.

The burden of coronary heart disease (CHD) is increasing at a greater rate in South Asia than in any other region globally, but there is little direct evidence about its determinants. The Pakistan Risk of Myocardial Infarction Study (PROMIS) is an epidemiological resource to enable reliable study of genetic, lifestyle and other determinants of CHD in South Asia. By March 2009, PROMIS had recruited over 5,000 cases of first-ever confirmed acute myocardial infarction (MI) and over 5,000 matched controls aged 30-80 years. For each participant, information has been recorded on demographic factors, lifestyle, medical and family history, anthropometry, and a 12-lead electrocardiogram. A range of biological samples has been collected and stored, including DNA, plasma, serum and whole blood. During its next stage, the study aims to expand recruitment to achieve a total of about 20,000 cases and about 20,000 controls, and, in subsets of participants, to enrich the resource by collection of monocytes, establishment of lymphoblastoid cell lines, and by resurveying participants. Measurements in progress include profiling of candidate biochemical factors, assay of 45,000 variants in 2,100 candidate genes, and a genomewide association scan of over 650,000 genetic markers. We have established a large epidemiological resource for CHD in South Asia. In parallel with its further expansion and enrichment, the PROMIS resource will be systematically harvested to help identify and evaluate genetic and other determinants of MI in South Asia. Findings from this study should advance scientific understanding and inform regionally appropriate disease prevention and control strategies.

High prevalence of lack of knowledge of symptoms of acute myocardial infarction in Pakistan and its contribution to delayed presentation to the hospital.

BACKGROUND: We conducted an observational study to determine the delay in presentation to hospital, and its associates among patients experiencing first Acute Myocardial Infarction (AMI) in Karachi, Pakistan. METHODS: A hospital based cross-sectional study was conducted at National Institute of Cardiovascular Disease (NICVD) in Karachi. A structured questionnaire was used to collect data. The primary outcome was delay in presentation, defined as a time interval of six or more hours from the onset of symptoms to presentation to hospital. Logistic regression analysis was performed to determine the factors associated with prehospital delay. RESULTS: A total of 720 subjects were interviewed; 22% were females. The mean age (SD) of the subjects was 54 (+/- 12) years. The mean (SE) and median (IQR) time to presentation was 12.3 (1.7) hours and 3.04 (6.0) hours respectively. About 34% of the subjects presented late. Lack of knowledge of any of the symptoms of heart attack (odds ratio (95% CI)) (1.82 (1.10, 2.99)), and mild chest pain (10.05 (6.50, 15.54)) were independently associated with prehospital delay. CONCLUSION: Over one-third of patients with AMI in Pakistan present late to the hospital. Lack of knowledge of symptoms of heart attack, and low severity of chest pain were the main predictors of prehospital delay. Strategies to reduce delayed presentation in this population must focus on education about symptoms of heart attack.

High rates of obesity and cardiovascular disease risk factors in lower middle class community in Pakistan: the Metroville Health Study.

OBJECTIVES: To describe the distribution of over weight and body mass index, waist circumference and waist/ hip ratio, correlate obesity measures to coronary heart disease risk factors in comparison to Pakistan National Survey (PNS). METHODS: The Metroville Health Study (MHS) was an urban risk factor reduction intervention study in Metroville Karachi. Base line data was used which was not a random sample. Demographic data including serum cholesterol, glucose, haemoglobin, and blood pressure were collected. RESULTS: In MHS high cholesterol was 16% and 24% in men and women respectively, and 25% had hypertension. Self-reported diabetes was 8%, over-weight/obesity 34% and 49% for men and women, compared to 16% and 25% for PNS, while high risk waist-hip ratio (WHR) was present in 41% and 72% of men and women respectively. Under-weight in Metroville men was 12% and 9% in women, compared to 26% and 27% in PNS. The anthropometry variables were significantly correlated with each other while weight was significantly correlated with TC and waist circumference (WC). CONCLUSION: Obesity was alarmingly prevalent in urban Metroville in comparison to PNS. Cardio Vascular Disease (CVD) risk factors were prevalent in Metroville and TC and WC were significantly correlated with obesity measures. For prevention of increasing CVD in urban communities, targeted programs of intervention are required.

Knowledge of modifiable risk factors of heart disease among patients with acute myocardial infarction in Karachi, Pakistan: a cross sectional study.

BACKGROUND: Knowledge is an important pre-requisite for implementing both primary as well as secondary preventive strategies for cardiovascular disease (CVD). There are no estimates of the level of knowledge of risk factor of heart disease in patients with CVD. We estimated the level of knowledge of modifiable risk factors and determined the factors associated with good level of knowledge among patients presenting with their first acute myocardial infarction (AMI) in a tertiary care hospital in Karachi, Pakistan. METHODS: A hospital based cross-sectional study was conducted at the National Institute of Cardiovascular Disease, a major tertiary care hospital in Karachi Pakistan. Patients admitted with their first AMI were eligible to participate. Standard questionnaire was used to interview 720 subjects. Knowledge of four modifiable risk factors of heart disease: fatty food consumption, smoking, obesity and exercise were assessed. The participants knowing three out of four risk factors were regarded as having a good level of knowledge. A multiple logistic regression model was constructed to identify the determinants of good level of knowledge. RESULTS: The mean age (SD) was 54 (11.66) years. A mere 42% of our study population had a good level of knowledge. In multiple logistic regression analysis, independent predictors of "good" level of knowledge were (odds ratio [95% confidence interval]) more than ten years of schooling were 2.5 [1.30, 4.80] (verses no schooling at all) and nuclear family system (verses extended family system) 2.54 [1.65, 3.89]. In addition, Sindhi ethnicity OR [3.03], higher level of exercise OR [2.76] and non user of tobacco OR [2.53] were also predictors of good level of knowledge. CONCLUSION: Our findings highlight the lack of good level of knowledge of modifiable risk factors for heart disease among subjects admitted with AMI in Pakistan. There is urgent need for aggressive and targeted educational strategies in the Pakistani population.

Process, rationale, and interventions of Pakistan's National Action Plan on Chronic Diseases.

Most developing countries do not comprehensively address chronic diseases as part of their health agendas because of lack of resources, limited capacity within the health system, and the threat that the institution of national-level programs will weaken local health systems and compete with other health issues. An integrated partnership-based approach, however, could obviate some of these obstacles. In Pakistan, a tripartite public-private partnership was developed among the Ministry of Health, the nongovernmental organization (NGO) Heartfile, and World Health Organization. This was the first time an NGO participated in a national health program; NGOs typically assume a contractual role. The partnership developed a national integrated plan for health promotion and the prevention and control of noncommunicable diseases (NCDs), which as of January 2006 is in the first stage of implementation. This plan, called the National Action Plan on NCD Prevention, Control, and Health Promotion (NAP-NCD), was released on May 12, 2004, and attempts to obviate the challenges associated with addressing chronic diseases in countries with limited resources. By developing an integrated approach to chronic diseases at several levels, capitalizing on the strengths of partnerships, building on existing efforts, and focusing primary health care on chronic disease prevention, the NAP-NCD aims to mitigate the effects of national-level programs on local resources. The impact of the NAP-NCD on population outcomes can only be assessed over time. However, this article details the plan's process, its perceived merits, and its limitations in addition to discussing challenges with its implementation, highlighting the value of such partnerships in facilitating the missions and mandates of participating agencies, and suggesting options for generalizability.

Competency profile of locally manufactured clopidogrel Lowplat and foreign manufactured clopidogrel Plavix in patients of suspected ischemic heart disease (CLAP-IHD).

OBJECTIVE: The primary objective of this study was to test the hypothesis that the antiplatelet effects of loading dose of locally manufactured clopidogrel Lowplat referred as drug (B) 600 mg (8 tablets) given once is comparable to the antiplatelet effects of loading dose of foreign manufactured clopidogrel Plavix referred as drug (A) 600 mg (8 tablets) given once in patients with suspected ischemic heart disease. METHODS: This was a double blind, randomized, cross over, study, to compare the safety and efficacy of study drug (B) versus (A) in adult subjects suffering from suspected ischemic heart disease presented at National Institute of Cardiovascular Disease (NICVD), Karachi. RESULTS: Mean platelet aggregation inhibition by drug (B) was 60.7% (p<0.001), while with drug (A) it was 57.8% (p<0.001), using 20 micromol/L ADP, which is statistically significant and comparable. Clopidogrel 600 mg as loading dose was well tolerated. CONCLUSION: Both drugs were equally effective in reducing the platelet aggregation. CLAP-IHD confirmed that drug (B) and (A) are equally effective and comparable antithrombotics in Pakistani population. The cost benefit of drug (B) should be made beneficial to the patients.

Blood pressure and hypertension distribution in a lower middle class urban community in Pakistan.

OBJECTIVE: To determine the awareness level, blood pressure profile and its correlates in Metroville Health Study and to compare the results with those of Pakistan National Health Survey and National Health and Nutrition Examination Survey of USA. METHODS: Sample consisted of 400 households of Metroville, included after informed consent. Demographic data was collected and Blood pressure, Cholesterol, Blood Glucose, Height and weight were measured. Obesity was calculated as BMI. The results were compared with those of the Pakistan National Health Survey and National Health and Nutrition Examination Survey of USA. RESULTS: For both sexes and all age groups, hypertension was more prevalent in MHS than Pakistan National Health Survey (PNHS) and U.S. MHS hypertensives were more likely to be aware of and treated for their condition than hypertensives of PNHS, but less likely than U.S. hypertensives. Systolic and diastolic blood pressure (DBP) rose with increased age in all three populations. Blood pressure also rose with increased body mass index (BMI) in MHS as well as PNHS and NHANES, with little differences in the degree of rise among them. A one-kg/Height (in m approximately) increment in BMI was associated with a 0.40-0.67 mmHg increment in systolic pressure in men and a 0.56-0.74 mmHg increment in women. The main difference between USA and two Pakistani surveys was the level of DBP, which was significantly higher in Pakistani Surveys than NHANES, for both men and women. CONCLUSIONS: The prevalence of Hypertension in Metroville was high. It showed a quantitative relationship to increasing age and BMI. Hypertension and obesity were the major public health problems in the lower middle class community of Metroville. It is recommended that awareness should be increased and preventive measures implemented.

Greek technique for type 4a coronary artery bifurcation lesions.

In routine coronary angiography, bifurcation lesion is not uncommon. Current practice of dealing with type 4a coronary bifurcation lesions (lesions of main branch without significant lesions of the side branch) may lead to true bifurcation lesions after stenting due to axial plaque redistribution. This series describes an experience with Greek technique for treatment of type 4a bifurcation lesions in 18 patients for primary stenting of main vessel with simultaneous kissing balloon of side branch in an effort to avoid snow plough effect.

Evaluation and comparison of blood pressure profiles of Pakistani cohort of children.

OBJECTIVE: To determine the blood pressure profile of children in Metroville, a lower middle class urban community of Karachi, Pakistan, and compare it to Pakistan National Health Survey of children. DESIGN: A research survey. PLACE AND DURATION OF STUDY: The study was conducted by National Institute of Cardiovascular Diseases, Karachi from 1996 2002. SUBJECTS AND METHODS: The blood pressure data was generated at the base line examination of MHS and was used to define the BP profile of urban Metroville children, age 2-17 years. Similar data of Pakistan National Health Survey (PNHS) undertaken by Pakistan Medical Research Council (PMRC), was used for comparison. RESULTS: A comparison of the blood pressure profile of the MHS with that of the PMRC showed that blood pressure was lower in the MHS. Additionally, comparison of the PMRC profile with USA data showed higher diastolic pressure in the PMRC. Comparison of Pakistani profiles with European data also showed higher blood pressure in Pakistani children. CONCLUSION: It is concluded that the MHS represents the BP profile of children in newly emerging lower middle class urban communities in Pakistan. PMRC data represents national average and can be used to define the blood pressure characteristics of urban communities similar to Metroville. The comparison with affluent countries highlighted the urgent need for community based preventive programs to combat hypertensive diseases in Pakistan.

The National Action Plan for the Prevention and Control of Non-communicable Diseases and Health Promotion in Pakistan--Cardiovascular diseases.

The National Action Plan for Non-Communicable Disease Prevention, Control and Health Promotion in Pakistan (NAP-NCD) incorporates prevention and control of cardiovascular diseases (CVD) as part of a comprehensive and integrated non-communicable Disease (NCD) prevention effort. In this programme, surveillance of cardiovascular risk factors is part of an integrated population-based NCD surveillance system. The population approach to CVD prevention is a priority area in this programme with a focus on broad policy measures and behavioural change communication. The former include revision of the current policy on diet and nutrition to expand its focus on under-nutrition; the development of a physical activity policy; strategies to limit the production of, and access to, ghee as a medium for cooking and agricultural and fiscal policies that increase the demand for, and make healthy food more accessible. The programme focuses attention on improving the quality of prevention programmes within primary and basic health sites and integrates concerted primary and secondary prevention programmes into health services as part of a comprehensive and sustainable, scientifically valid, and resource-sensitive programme for all categories of healthcare providers. It promotes screening for raised blood pressure at the population level and screening for dyslipidaemia and diabetes in high-risk groups only. It highlights the need to ensure the availability of aspirin, beta blockers, thiazides, ACE inhibitors, statins and penicillin at all levels of healthcare. The programme points out the need to conduct clinical end-point trials in the native Pakistani setting to define cost-effective therapeutic strategies for primary and secondary prevention of CVDs. Emphasis is laid on building capacity of health systems in support of CVD prevention and control and building a coalition or network of organizations to add momentum to CVD prevention and control efforts.

Short- and intermediate-term follow-up results of percutaneous transluminal balloon valvuloplasty in adolescents and young adults with congenital pulmonary valve stenosis.

Percutaneous pulmonary balloon valvuloplasty (PBV) is a well-established treatment alternative to surgery in many cardiology centers. We described our experience with PBV in 25 adolescent and young adult patients with isolated pulmonary valve stenosis (PVS). Among 20 successful PBVs, there was a significant immediate decrease in right ventricular systolic pressure from 116.9 32.4 mmHg to 60.5 18.7 mmHg (p < 0.0001) and a decrease in transpulmonary valve pressure gradient from 93.5 32.8 mmHg to 33.5 9.7 mmHg (p < 0.0001) was noted. The follow-up period was 1-5 years (mean = 3.2 1.2 years), during which patients were periodically assessed by Doppler echocardiogram. During follow-up, the transpulmonary valve pressure gradient further decreased from 33.5 9.7 mmHg to 18.6 3.4 mmHg (p < 0.0001) mainly due to regression of infundibular hypertrophy. Thus, the study showed excellent short-term and intermediate-term results of PBV.