Ahmad Al-Sarraf

Incidence of pancreatitis, secondary causes, and treatment of patients referred to a specialty lipid clinic with severe hypertriglyceridemia: a retrospective cohort study

BackgroundSevere hypertriglyceridemia (HTG) is one cause of acute pancreatitis, yet the level of plasma triglycerides likely to be responsible for inducing pancreatitis has not been clearly defined.Methods and ResultsA retrospective cohort study was conducted on patients presenting non-acutely to the Healthy Heart Program Lipid Clinic at St. Pauls Hospital with a TG level > 20 mM (1772 mg/dl) between 1986 and 2007. Ninety-five patients with TG > 20 mM at the time of referral were identified, in who follow up data was available for 84. Fifteen patients (15.8%), with a mean outpatient TG level of 38.1 mM, had a history of acute pancreatitis. Among 91 additional patients with less severe HTG, none had a history of pancreatitis when TG were between 10 and 20 mM. Among patients with TG > 20 mM on presentation, 8 (8.5%), with a mean TG level of 67.8 mM, exhibited eruptive xanthomata. A diet high in carbohydrates and fats (79%) and obesity (47.6%) were the two most frequent secondary causes of HTG at initial visit. By 2009, among patients with follow up data 53% exhibited either pre-diabetes or overt Type 2 diabetes mellitus. Upon referral only 23 patients (24%) were receiving a fibrate as either monotherapy or part of combination lipid-lowering therapy. Following initial assessment by a lipid specialist this rose to 84%, and remained at 67% at the last follow up visit.ConclusionsThese results suggest hypertriglyceridemia is unlikely to be the primary cause of acute pancreatitis unless TG levels are > 20 mM, that dysglycemia, a diet high in carbohydrates and fats, and obesity are the main secondary causes of HTG, and that fibrates are frequently overlooked as the drug of first choice for severe HTG.

Cardiovascular risk and atherosclerosis prevention

Until recently, coronary artery disease (CAD) was the leading cause of death in the developed countries. Its remarkable decline can be attributed to our knowledge of the major risk factors identified by several studies resulting in better prevention and treatment. Of the major risk factors, the ratio of apolipoprotein (apo) B/apo A1 followed by smoking, diabetes, and hypertension are the most important. A number of risk scores for men and women are now available to estimate the likelihood of development of CAD. However, because of the risk of CAD differs in various populations, some of the algorithms are more appropriate for some countries but not suitable for others. These risk assessment algorithms differ in the parameters they use. All the risk scores have some limitations such as different study populations; the age of the study is also different, and number of points awarded for age categories also differs among the various algorithms. In an effort to further improve the risk prediction, a number of biomarkers have been studied. In addition to plasma lipids, a lot of interest has focused on apo measurements; particularly of apo B. Another valuable biomarker is lipoprotein (a) [Lp(a)]. Lp(a) is not only atherogenic as low-density lipoprotein (LDL) but also prothrombotic, and several studies indicate that Lp(a) is an independent risk factor for CAD. The lipid profile provides a framework for appropriate management. This includes therapeutic lifestyle changes and medications. Lifestyle interventions are the cornerstone of CAD prevention strategies and are the first step in risk factor management. Of particular importance are smoking cessation, achievement and maintenance of ideal body weight, regular exercise, reduction in the intake of saturated fat and sugars, and decreasing level of stress. Of medications, lipid-lowering, anti-hypertensive, and anti-coagulant can be effectively used. The current strategies for risk assessment and prevention have been very successful contributing to the more than 50% decrease in CAD mortality over the last 20 years. Thus, in Canada, cardiovascular disease is no longer the leading cause of death.

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.

Complete Apo AI deficiency in an Iraqi Mandaean family: case studies and review of the literature.

Complete apo A1 deficiency is a rare genetic disorder that has been associated with premature atherosclerosis. We describe a family of Iraqi Mandaean background with complete apo A1 deficiency caused by a new nonsense mutation in the APOA1 gene. Interestingly, there were marked differences in the clinical presentation of the two homozygotes in this family. A 35-year-old woman presented with xanthelasmas and xanthomas but showed only minimal changes on cardiovascular examinations and no clinical symptoms. However, her 37-year-old brother was diagnosed with myocardial infarction at age 35. In addition, both the homozygotes had elevated C-reactive protein levels. The C-reactive protein levels increased three-fold during pregnancy, then decreased postpartum and further decreased with statin treatment. Cholesterol ester transfer protein mass was close to the upper reference range, whereas the activity was low, likely because of the lack of the substrate. Here, we characterize the phenotype and genotype of the first Middle Eastern family with apo A1 deficiency and compare and contrast the findings in the two homozygous siblings and review the previously reported cases of apo A1 deficiency.

Regional and National Familial Hypercholesterolemia Registries: Present International Application, Importance, and Needs for Canada

Cardiovascular disease (CVD) is the leading cause of death in the Western world. Atherosclerosis is the most common pathological vascular change underlying CVD with hypercholesterolemia constituting a major risk factor. Heterozygous familial hypercholesterolemia (FH) is a common autosomal dominant disease with a prevalence of 1:500 in the general population. Thus, approximately 13 million people worldwide and 68,000 in Canada are carriers of an FH gene. FH is caused by loss-offunction mutations in the low-density lipoprotein (LDL) receptor or apolipoprotein B-100 gene, or gain-of-function mutations in proprotein convertase subtilisin/kexin type 9, resulting in very high blood cholesterol levels and premature CVD. It is clinically characterized by arcus cornealis and tendon xanthomas, more common among people of French Canadian, Christian Lebanese, and Afrikaner descent. If undiagnosed and untreated, the cumulative risk of coronary artery disease by age 60 is more than 60% among men and 30% among women. In contrast to many other genetic diseases, treatment in the form of lifestyle management and lipid-lowering medications is highly effective in preventing not only CVD but also total morbidity and mortality. Not infrequently, FH is diagnosed only after a major cardiovascular event; therefore implementation of nationwide screening is warranted to allow early diagnosis and treatment. Despite an international effort to improve the identification and management of FH patients, only a few countries (The Netherlands, Spain, and Wales) have large-scale programs to systematically determine the FH status of relatives of FH patients. Although FH is more common than type 1 diabetes mellitus, both lay people and health professionals lack awareness of FH, its diagnostic features, and consequences. Framingham-based cardiovascular risk assessment should not be used in individuals with extreme hypercholesterolemia, but health professionals may still reassure FH patients

Fish odour syndrome

A 68-year-old woman with familial hyper-cholesterolemia and osteoarthritis was treated with atorvastatin 10 mg daily for four months, ending in October 2006. At that time, hypothyroidism was diagnosed, and the atorvastatin was temporarily discontinued. She returned to our lipid clinic in September

Low prevalence of type 2 diabetes mellitus among patients with high levels of high-density lipoprotein cholesterol

BACKGROUND Diabetes mellitus and low levels of high-density lipoprotein cholesterol (HDL-C) are among several known risk factors for coronary artery disease. Recent research has shown potential mechanistic links between these two diseases. OBJECTIVES The aim of our study was to characterize, by examining particular coronary artery disease risk factors, patients with extremely high and low levels of HDL-C who were referred to a prevention clinic. METHODS We compared the phenotypes of 113 patients with HDL-C levels greater than the 90th percentile with 212 patients with levels less than the 10th percentile by using a retrospective chart review. RESULTS The cohort with high HDL-C had a remarkable difference in the incidence of type 2 diabetes (1.8% vs 21.7%). The high HDL-C cohort also had a greater age (52.1 years vs 46.7 years), more light or moderate alcohol consumption (70.8% vs 49.4%), more healthy diet (30.1% vs 22.4%), more light or moderate exercise (90.8% vs 52.2%), and a lower body mass index (25.2 kg/m² vs 28.1 kg/m²). CONCLUSIONS Compared with the low HDL-C group--and also the general population--the high HDL-C cohort had a remarkably low prevalence of diabetes mellitus.

Statin resistant dyslipidemia in a patient treated with amiodarone.

The authors describe a patient treated with amiodarone presented with high low-density lipoprotein cholesterol (LDL-C) levels who did not respond to treatment with a statin. Both amiodarone and amiodarone induced hypothyroidism influence the synthesis of LDL-receptor which may explain the lack of effect of statin. This was confirmed by normalisation of LDL-C upon discontinuation of amiodarone and treatment with thyroxine.

Bisalbuminuria detected by agarose gel electrophoresis

Bisalbuminuria is a rare condition characterized by the presence of two distinct fractions of urinary albumin on electrophoresis. While many cases of bisalbuminemia have been reported there are only a few reports of bisalbuminuria [1–3]. Urinary albumin can dimerize when it is stored at−14 °C in urine with high protein content or if the patient is on steroids [4]. We report the presence of a dimerized albumin in freshly voided urine from a patient who was not taking steroid or any other drug known to be associated with the presence of a dimerized albumin. The patient was an 82–year-old Canadian aboriginal woman who presented with multiple problems that included ischemic heart disease, type 2 diabetes, chronic renal failure, hyperlipidemia, hypothyroidism, hypertension and chronic obstructive pulmonary disease. She was taking levothyroxine, temazepam, lisinopril, amlodipine, plavix,metoprolol, lasix, insulin and ventolin. Shewas admitted for hip fracture, underwent surgery and was discharged from hospital after a few weeks in a stable condition.

Hepatic lipase deficiency in a Middle-Eastern-Arabic male

Hepatic lipase (HL) deficiency is a rare genetic disorder that has been associated with premature atherosclerosis despite high plasma high-density lipoprotein (HDL) cholesterol concentrations in the affected individuals. The authors describe the clinical and biochemical features of HL deficiency in a young male of Middle-Eastern-Arabic origin. This is the first report of cholesterol ester transfer protein (CETP) activity and mass in HL deficiency in a patient from this ethnic group. While the CETP mass was high, its activity was low, a discrepancy likely due to the abnormal composition of patients HDL particles.