Usman Ahmad

Factors Associated with Adherence to Anti-Hypertensive Treatment in Pakistan

Objectives Poor adherence is one of the biggest obstacles in therapeutic control of high blood pressure. The objectives of this study were (i) to measure adherence to antihypertensive therapy in a representative sample of the hypertensive Pakistani population and (ii) to investigate the factors associated with adherence in the studied population. Methods and Results A cross-sectional study was conducted on a simple random sample of 460 patients at the Aga Khan University Hospital (AKUH) and National Institute of Cardiovascular Diseases, Karachi, from September 2005–May 2006. Adherence was assessed using the Morisky Medication Adherence Scale (MMAS), with scores ranging from 0 (non-adherent) to 4 (adherent). In addition to MMAS, patient self-reports about the number of pills taken over a prescribed period were used to estimate adherence as a percentage. AKU Anxiety and Depression Scale (AKU-ADS) was incorporated to find any association between depression and adherence. At a cut-off value of 80%, 77% of the cases were adherent. Upon univariate analyses, increasing age, better awareness and increasing number of pills prescribed significantly improved adherence, while depression showed no association. Significant associations, upon multivariate analyses, included number of drugs that a patient was taking (P<0.02) and whether he/she was taking medication regularly or only for symptomatic relief (P<0.00001). Conclusions Similar to what has been reported worldwide, younger age, poor awareness, and symptomatic treatment adversely affected adherence to antihypertensive medication in our population. In contrast, monotherapy reduced adherence, whereas psychosocial factors such as depression showed no association. These findings may be used to identify the subset of population at risk of low adherence who should be targeted for interventions to achieve better blood pressure control and hence prevent complications.

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=2×10−3) 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=1×10−3 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. Conclusion—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.

Strong association of a renin intronic dimorphism with essential hypertension.

The objectives of this project were two-fold: to identify the genetic mutation that has been detected as an MboI dimorphism in intron 9 of the human renin (REN) gene and to confirm a previously reported, putative association between the REN MboI dimorphism and clinical diagnosis of essential hypertension (EHT) in a population of Gulf Arabs from the United Arab Emirates. Sequencing of the MboI dimorphic site was carried out on DNA of randomly chosen cases and controls. A retrospective case-control study was carried out in 689 unrelated subjects (326 first-time, clinically diagnosed hypertensives and 363 age- and gender-matched normotensive subjects), selected from the resident population of the Abu Dhabi Emirate. A polymerase chain reaction/MboI-RFLP based method was employed to compare genotype and allele distributions. Nucleotide sequences at the MboI site of the cut and uncut alleles were determined to be GATC and GGTC, respectively. This A>G mutation is located 10,631 base pairs (bp) 3′ to the start of the REN gene, and 79 bp 3′ to the end of exon 9. The genotype distributions of the REN 10631A>G dimorphism were found to be significantly different between hypertensive and normotensive subjects (χ2= 42.29, df=2, p<0.001). Frequencies of A alleles were 0.54 in EHT vs. 0.37 in normotensive subjects, which is even more demarcated than what was found previously. The frequency of AA genotypes was higher in the hypertensive group than in the normotensive group (34.7% vs. 14.0%). The quantification of the association of A alleles with increased risk of EHT was assessed with corresponding odds ratios (OR), which gave the following values: OR of GG vs. AG genotypes, 1.3 (95% confidence interval [CI]: 0.90–1.88); OR of GG vs. AA, 3.75 (95% CI: 2.41–5.86). In conclusion, REN 10631A alleles are significantly associated with EHT in the Emirati population. This has now been found in two different and therefore independent sample populations from the Abu Dhabi Emirate. Moreover, this genetic effect seems to be acting in a recessive fashion. Hence, either the REN gene itself, or another gene that is in linkage disequilibrium with REN 10631A>G, is implicated in the pathogenesis of EHT in Emirati.

Persistent left superior vena cava (PLSVC) with anomalous left hepatic vein drainage into the right atrium: role of imaging and clinical relevance

Persistent left superior vena cava (PLSVC) is a very rare and yet the most commonly described thoracic venous anomaly in medical literature. It has a 10-fold higher incidence with congenital heart disease. PLSVC often becomes apparent when an unknown PLSVC is incidentally discovered during central venous line placement, intracardiac electrode/pacemaker placement or cardiopulmonary bypass, where it may cause technical difficulties and life-threatening complications. PLSVC is also associated with disturbances of cardiac impulse formation and conduction including varying degrees of heart blocks, supraventricular arrhythmias and Wolff Parkinson White syndrome. We describe the case of an 86-year-old male with a history of coronary artery disease and chronic atrial fibrillation who presented with worsening dyspnea and syncopal episodes. An ECG was consistent with complete heart block. During lead placement for the pacemaker, a left subclavian approach was unsuccessful. A left venogram was performed through the brachial vein that demonstrated a left superior vena cava. The diagnosis was confirmed with echocardiography using a bubble study and also a chest CT. The anatomy was unique as there was anomalous left hepatic vein drainage into the right atrium. The case provides insight into the diagnostic modalities and clinical considerations of this unusual thoracic venous anomaly.

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.

Outcomes for Lung Transplantation for Lung Cancer in the United Network for Organ Sharing Registry

BACKGROUND Advanced bronchoalveolar carcinoma (BAC) carries a poor prognosis, with median survival of approximately 1 year. More extended survivals have been reported after lung transplantation for BAC; however, fewer than 50 patients have been reported. To compare outcomes of lung transplantation for advanced BAC, we studied this population in a compulsory, prospectively maintained database. METHODS The United Network for Organ Sharing (UNOS) database was queried for patients undergoing lung transplant from 1987 to 2010 for the diagnosis of BAC or cancer. Pathology reports of explanted specimens were reviewed. RESULTS Twenty-nine patients underwent lung transplantation for BAC, representing 0.13% of the 21,553 lung transplants during the study period. BAC patients had better forced expiratory volume in 1 second percent predicted (60% vs 35%, p<0.0001) and received more double-lung transplants (79% vs 54%, p=0.006). Pure BAC was present in only 52% of the explants, whereas 41% had some degree of invasive tumor, and 7% had pure adenocarcinoma. The BAC and general lung transplantation cohorts had similar 30-day mortality (10% vs 7%, p=0.44) and 5-year survival (57% vs 50%, p=0.66). CONCLUSIONS Survival after lung transplantation for BAC appears to be consistent with that of lung transplantation for other diagnoses and is better than that reported with chemotherapy. Further study is warranted to identify the subgroup of patients with lung cancer who will have a maximum survival advantage after lung transplantation.

Attitudes towards Genetic Diagnosis in Pakistan: A Survey of Medical and Legal Communities and Parents of Thalassemic Children

Objectives: It was the aim of this study to assess the attitudes of doctors, medical students, lawyers, parliament members and parents of thalassemic children towards genetic diagnosis in Pakistan. Study Design: A cross-sectional descriptive survey was conducted among representative samples. Results: Five hundred and seventy doctors, 49 lawyers, 178 medical students, 89 parents of thalassemic children and 16 members of parliament (MPs) were included in the survey. The groups showed considerable difference in their attitudes towards different aspects of the issue. A large proportion (88.5%) agreed to the idea of genetic diagnostic screening, especially the parents of thalassemic patients. Premarital carrier screening was favored by 77% of the respondents. Prenatal screening was most favored by the parents of thalassemic children (94.4%). Likewise, a majority of parents of thalassemic children were in favor of abortion in case of an affected fetus. Genetic self-screening was also favored most by the parents of thalassemic patients (78.2%). Only 24% of the doctors favored making genetic screening mandatory, whereas 63% of the parents agreed to the idea. Conclusion: Attitudes regarding genetic diagnosis are markedly different among various societal groups in Pakistan. The parents of the affected children strongly favor genetic screening as does the medical community, though not as strongly as the parents. The legislative groups, particularly the MPs, are reserved in their support. Genetic diagnosis can help decrease the disease burden in the future. However, it raises a number of ethical issues, which need to be addressed. It is important to educate the population about potential benefits as well as ethical dilemmas involved so that the general public is able to make the right decisions for themselves and their families.

Current Status of Lung Cancer Screening

Recent results have demonstrated a major reduction in lung cancer mortality through computed tomography screening and no benefit from chest radiograph (CXR) screening. This presents a huge potential for benefit but also poses challenges regarding management of details to minimize harm. Many unresolved questions remain that must be addressed to implement computed tomography screening for lung cancer in a thoughtful and responsible way.

Current Readings: The Most Influential and Recent Studies Involving Surgical Management of Thymoma

Thymic epithelial tumors can be challenging to manage because of local invasion of mediastinal structures and high recurrence rates. Surgery is the mainstay of treatment and complete resection is associated with the best prognosis. Although practices vary, neoadjuvant chemotherapy is often used to improve resectability. Extended resections following neoadjuvant treatment have been safely performed for locally advanced tumors. R0 resection should be the goal and should dictate the surgical approach and extent of resection. Postoperative radiation therapy has often been used to reduce the risk of recurrence after resection. No study has definitively shown a recurrence or survival benefit with postoperative radiation therapy in completely resected tumors. However, there are some data to support its use in patients with residual disease. As our knowledge has largely been derived from small series, larger multicenter collaborative efforts are needed to improve our understanding of this disease.

Evaluation of therapeutic control in a Pakistani population with hypertension

RATIONALE, AIMS AND OBJECTIVES Cardiovascular diseases (CVD) are increasing at an alarming rate in South Asia. High blood pressure is a modifiable risk factor for CVD. In this study, we evaluated the control of blood pressure and the prevalence of cardiovascular risk factors in patients with hypertension. METHOD A cross-sectional study was conducted in 50 primary health care centres throughout Pakistan. Individuals with a documented history of hypertension, receiving pharmacological therapy, were enrolled and evaluated for the control of their blood pressure. RESULTS The recommended therapeutic control of hypertension (systolic blood pressure <140 mmHg, diastolic blood pressure <90 mmHg) was seen in only 6.4% of the study participants. Values of both the mean systolic and diastolic blood pressures in all subjects were higher than the desired therapeutic levels (P<0.001). There was a high prevalence in the study population of established but modifiable risk factors of CVD, such as smoking (30.5%), hypercholesterolemia (59.5%) and sedentary lifestyle (43.5%). Lack of therapeutic control of systolic blood pressure was found significantly associated with age, hypercholesterolemia and sedentary lifestyle (P<0.05). CONCLUSIONS Patients being treated at primary health care centres in Pakistan have inadequate control of high blood pressure. Evidence-based continuous education of primary health care physicians is a necessary intervention for optimizing treatment strategies and achieving better therapeutic control of hypertension in our population.