Yajnavalka Banerjee

Familial hypercholesterolemia mutations in the Middle Eastern and North African region: A need for a national registry

BACKGROUND Familial hypercholesterolemia (FH) is a well-understood Mendelian disorder that increases the risk of cardiovascular disease (CVD), a leading cause of mortality in Middle Eastern and North African (MENA) countries. OBJECTIVE Review the reporting status of FH mutations across MENA and propose a systemic and strategic method for building a MENA FH registry. METHODS Systematic literature search for statistics pertaining to CVD and comparison of number of FH mutations reported in MENA countries and countries with established FH registries. RESULTS Only 57 mutations were reported in 17 MENA countries, whereas more than 500 mutations reported in 3 Western countries. Mortality rates due to CVD were significantly higher in MENA countries compared with Western countries. CONCLUSIONS The relatively low reporting of FH mutations in the consanguineous MENA communities with higher prevalence of CVD indicates poor awareness of CVD genetic risk and warrants a registry to prevent premature CVD due to FH. This registry will help in identifying novel and reported FH mutations, all of which will have clinical and research benefits in MENA countries.

Saphenous vein graft vs. radial artery graft searching for the best second coronary artery bypass graft

Coronary artery bypass grafting (CABG) was first used in the late 1960s. This revolutionary procedure created hope among ischemic heart disease patients. Multiple conduits are used and the golden standard is the left internal mammary artery to the left anterior descending artery. Although all approaches were advocated by doctors, the use of saphenous vein grafts became the leading approach used by the majority of cardiac surgeons in the 1970s. The radial artery graft was introduced at the same time but was not as prevalent due to complications. It was reintroduced into clinical practice in 1989. The procedure was not well received initially but it has since shown superiority in patency as well as long-term survival after CABG. This review provides a summary of characteristics, technical features and patency rates of the radial artery graft in comparison with venous conduits. Current studies and research into radial artery grafts and saphenous vein grafts for CABG are explored. However, more studies are required to verify the various findings of the positive effects of coronary artery bypass grafting with the help of radial arteries on mortality and long-lasting patency.

Effect of a Natural Supplement Containing Curcuma Longa, Guggul, and Chlorogenic Acid in Patients With Metabolic Syndrome

The impact of a natural supplement (Kepar; Rikrea, Italy), containing several plant extracts such as curcuma longa, silymarin, guggul, chlorogenic acid, and inulin, was evaluated in 78 patients with metabolic syndrome (MetS; 45 men; age: 62 ± 9 years). Kepar at a dose of 2 pills/d was given for 4 months as add-on therapy to the ongoing treatment, maintained at fixed doses for the entire study. Anthropometric variables, plasma lipids, glucose parameters, and oxidative stress were measured at baseline and after 4 months. We found significant reductions in body weight (from 81.1 ± 13.5 to 79.4 ± 12.5 kg, P < .0001), body mass index (from 29.6 [23.7] to 29.3 [21.9] kg/m2, P = .001), and waist circumference (from 105 ± 11 to 102 ± 10 cm, P = .0004) as well as in fasting glucose (from 6.5 [11.7] to 6.4 [7.6] mmol/L, P = .014) and total cholesterol (from 4.8 ± 1.4 to 4.5 ± 1.0 mmol/L, P = .03). No significant changes were found in the other appraised parameters, including oxidative stress. In conclusion, after few months of treatment Kepar seems to exert beneficial effects in patients with MetS. Larger studies with a longer follow-up period are needed to confirm these preliminary findings.

First Case Report of Familial Hypercholesterolemia in an Omani Family Due to Novel Mutation in the Low-Density Lipoprotein Receptor Gene

Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder. Mutations have been found in at least 3 genes: the low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB), and proprotein convertase subtilisin/kexin type 9 (PCSK9). We report the first case of FH in an Omani family due to a novel mutation in the LDLR gene. A 9-year-old female was referred to our lipid clinic with eye xanthelasmata and thickening of both Achilles tendons. Evaluation of the lipid profile showed the off treatment total cholesterol of 896 mg/dL (23.2 mmol/L), low-density lipoprotein cholesterol (LDL-C) of 853 mg/dL (22.1 mmol/L), APOB of 4.5 g/L, triglyceride of 71 mg/dL (0.8 mmol/L), and high-density lipoprotein cholesterol of 0.74 mmol/L. Genetic analysis of the LDLR gene showed a homozygous frameshift deletion mutation (272delG) at exon 3. The female patient was treated with a combination of rosuvastatin/ezetimibe and LDL apheresis.

Identification and Treatment of Patients with Homozygous Familial Hypercholesterolaemia: Information and Recommendations from a Middle East Advisory Panel

We present clinical practice guidelines for the diagnosis and treatment of homozygous familial hypercholesterolaemia (HoFH) in the Middle East region. While guidelines are broadly applicable in Europe, in the Middle East we experience a range of confounding factors that complicate disease management to a point whereby the European guidance cannot be applied without significant modification. Specifically, for disease prevalence, the Middle East region has an established epidemic of diabetes and metabolic syndrome that can complicate treatment and mask a clinical diagnosis of HoFH. We have also a high incidence of consanguineous marriages, which increase the risk of transmission of recessive and homozygous genetic disorders. This risk is further augmented in autosomal dominant disorders such as familial 
hypercholesterolaemia (FH), in which a range of defective genes can be transmitted, all of which contribute to the phenotypic expression of the disease. In terms of treatment, we do not have access to lipoprotein apheresis on the same scale as in Europe, and there remains a significant reliance on statins, ezetimibe and the older plasma exchange methods. Additionally, we do not have widespread access to anti-apolipoprotein B therapies and microsomal transfer protein inhibitors. In order to adapt existing global guidance documents on HoFH to the Middle East region, we convened a panel of experts from Oman, Saudi Arabia, UAE, Iran and Bahrain to draft a regional guidance document for HoFH. We also included selected experts from outside the region. This panel statement will form the foundation of a detailed appraisal of the current FH management in the Middle Eastern population and thereby provide a suitable set of guidelines tailored for the region.

The Effect of Residing Altitude on Levels of High-Density Lipoprotein Cholesterol: A Pilot Study From the Omani Arab Population.

Lower mortality rates from coronary heart disease and higher levels of serum high-density lipoprotein cholesterol (HDL-C) have been observed in populations residing at high altitude. However, this effect has not been investigated in Arab populations, which exhibit considerable genetic homogeneity. We assessed the relationship between residing altitude and HDL-C in 2 genetically similar Omani Arab populations residing at different altitudes. The association between the levels of HDL-C and other metabolic parameters was also investigated. The levels of HDL-C were significantly higher in the high-altitude group compared with the low-altitude group. Stepwise regression analysis showed that altitude was the most significant factor affecting HDL-C, followed by gender, serum triglycerides, and finally the 2-hour postprandial plasma glucose. This finding is consistent with previously published studies from other populations and should be taken into consideration when comparing cardiovascular risk factors in populations residing at different altitudes.

Low-density lipoprotein receptor gene mutation analysis and structure-function correlation in an Omani arab family with familial hypercholesterolemia.

Familial hypercholesterolemia (FH) is an autosomal dominant disorder typified by elevated low-density lipoprotein cholesterol (LDL-C) levels caused by mutations in the LDL receptor (LDLR), apolipoprotein B (ApoB), or proprotein convertase subtilisin/kexin type 9 (PCSK9) genes. Previously, we reported a novel mutation in the exon-3 of LDLR gene, observed in a 9-year-old Omani Arab female. Here, we investigated the mode of inheritance of this mutation and confirmed that FH in this family is due to mutation only in the LDLR and not PCSK9 and ApoB genes. Further, the effect of the mutation has been appraised in silico on the tertiary structure of LDLR. A model of the mutant LDLR has been constructed using the coordinates of the wild-type LDLR extracellular domain. Based on the model, we present a mechanistic justification behind the observed detrimental effect of the mutation on LDL-C levels.

Protein anticoagulants targeting factor VIIa–tissue factor complex: a comprehensive review

Abstract Anticoagulants are pivotal for the treatment of debilitating thromboembolic and associated disorders. Current anticoagulants such as heparin and warfarin are non-specific and have a narrow therapeutic window. These limitations have provided the impetus to develop new anticoagulant therapies/strategies that target specific factors in the blood coagulation cascade, ideally those located upstream in the clotting process. Factor VIIa (FVIIa) presents an attractive target as it, in complex with tissue factor (TF), acts as the prima ballerina for the formation of blood clot. A comprehensive review delineating the structure–activity relationship of protein/peptide anticoagulants targeting FVIIa or TF–FVIIa complex is absent in the literature. In this article, we have addressed this deficit by appraising the peptide/protein anticoagulants that target FVIIa/TF–FVIIa complex. Further, the current status of these anticoagulants, with regard to their performance in different clinical trials has also been presented. Lastly, the unexplored domains of these unique proteins have also been highlighted, which will facilitate further translational research in this paradigm, to improve strategies to counter and treat thromboembolic disorders.

Quality of Diabetes Care in Primary Health Centres in North Al-Batinah of Oman

Objective: To assess the quality of diabetic care provided in primary health care settings in Oman. Methods: This was a cross-sectional study of randomly selected 500 patients with diabetes mellitus (DM) attending 6 primary care diabetic clinics in the north Al-Batinah region of Oman from January to December 2010. Nine standards on the quality of diabetes care were audited. Results: The mean age of the sample was 51±13 years, ranging from 15 to 87 years; the majority (61%) were females. The mean duration of DM was 4±3 years, ranging from 1 to 18 years. Seventy-seven percent of the patients attended diabetic clinics at least 4 times per year. Of the 9 assessed diabetic standards, HbA1c was documented in 33% of the patients, body mass index in 12%, low-density lipoprotein cholesterol (LDL-C) in 40%, urinary albumin:creatinine ratio in 28%, creatinine in 63% and blood pressure (BP) in 96%. Optimal control among the documented indicators was noted in 32, 21, 25, 85, 95 and 19%, respectively. Twenty percent of the patients had their ECGs done while only 39% of the patients had foot examination. No patient had attained control in all of HbA1c., BP and LDL-C. Conclusion: There is a gap between the recommended DM care guidelines and current practice with consequent poor quality of care in these patients.

Assays for drug resistant tuberculosis in high burden countries

Jessica Minion and colleagues have done a systematic review and meta-analysis to assess the accuracy of microscopic-observation drug susceptibility (MODS) and thin layer agar (TLA) in rapid screening of multidrug resistant (MDR) tuberculosis. However, the studies included in the investigation did not include those from countries that are most burdened by MDR tuberculosis. According to a WHO report that mapped the distribution of MDR tuberculosis cases, 27 countries account for about 85% of the estimated cases of multidrug resistance among new cases of tuberculosis. China and India have the most cases, whereas incidence of MDR tuberculosis in the USA is decreasing rapidly. In a country such as India, where about 42% of the population is below the poverty with the authors of published works, who were generally responsive. Grey literature refers to data that is not formally published in easily accessed sources, such as conference abstracts. Intervention studies that are published in grey literature are more likely to have negative results than those published in journals, and failure to include these sources signifi cantly aff ects the results of systematic reviews of interventions. It is not known if a similar bias applies to studies of diagnostic accuracy or prognosis from grey literature. We did not systematically search for unpublished studies, and this might be an additional limitation of our study.