Hyperlipidemias: Canada

McCrindle BW, Urbina EM, Dennison BA, Jacobson MS, Steinberger J, Rocchini AP, Hayman LL, Daniels SR, Anonymous00137, Anonymous00138, Anonymous00139. · Hospital for Sick Children, Toronto, Canada. · Circulation. · Pubmed #17377073 links to  free full text

Abstract: Despite compliance with lifestyle recommendations, some children and adolescents with high-risk hyperlipidemia will require lipid-lowering drug therapy, particularly those with familial hypercholesterolemia. The purpose of this statement is to examine new evidence on the association of lipid abnormalities with early atherosclerosis, discuss challenges with previous guidelines, and highlight results of clinical trials with statin therapy in children and adolescents with familial hypercholesterolemia or severe hypercholesterolemia. Recommendations are provided to guide decision-making with regard to patient selection, initiation, monitoring, and maintenance of drug therapy.

McPherson R, Frohlich J, Fodor G, Genest J, Canadian Cardiovascular Society. · University of Ottawa Heart Institute, Ottawa, Canada. · Can J Cardiol. · Pubmed #16971976 links to  free full text

Abstract: Since the last publication of the recommendations for the management and treatment of dyslipidemia, new clinical trial data have emerged that support a more vigorous approach to lipid lowering in specific patient groups. The decision was made to update the lipid guidelines in collaboration with the Canadian Cardiovascular Society. A systematic electronic search of medical literature for original research consisting of blinded, randomized controlled trials was performed. Meta-analyses of studies of the efficacy and safety of lipid-lowering therapies, and of the predictive value of established and emerging risk factors were also reviewed. All recommendations are evidence-based, and have been reviewed in detail by primary and secondary review panels. Major changes include a lower low-density lipoprotein cholesterol (LDL-C) treatment target (lower than 2.0 mmol/L) for high-risk patients, a slightly higher intervention point for the initiation of drug therapy in most low-risk individuals (LDL-C of 5.0 mmol/L or a total cholesterol to high-density lipoprotein cholesterol ratio of 6.0) and recommendations regarding additional investigations of potential use in the further evaluation of coronary artery disease risk in subjects in the moderate-risk category.

McAlister FA, Levine M, Zarnke KB, Campbell N, Lewanczuk R, Leenen F, Rabkin S, Wright JM, Stone J, Feldman RD, Lebel M, Honos G, Fodor G, Burgess E, Tobe S, Hamet P, Herman R, Irvine J, Culleton B, Petrella R, Touyz R, Anonymous00140. · Division of General Internal Medicine, University of Alberta, Edmonton, Canada. · Can J Cardiol. · Pubmed #11381277 links to  free full text

Abstract: OBJECTIVE: To provide updated, evidence-based recommendations for the therapy of hypertension in adults. OPTIONS: For patients with hypertension, there are a number of lifestyle manoeuvres and antihypertensive agents that may control blood pressure. Randomized trials evaluating first- line therapy with thiazides, beta-adrenergic antagonists, angiotensin-converting enzyme inhibitors, calcium channel blockers, alpha-blockers, centrally acting agents or angiotensin II receptor antagonists were reviewed. OUTCOMES: The health outcomes considered were changes in blood pressure, cardiovascular morbidity, and cardiovascular and/or all-cause mortality rates. Economic outcomes were not considered due to insufficient evidence. EVIDENCE: Medline searches were conducted from the period of the last revision of the Canadian Recommendations for the Management of Hypertension (May 1998 to October 2000). Reference lists were scanned, experts were polled, and the personal files of the subgroup members and authors were used to identify other studies. All relevant articles were reviewed and appraised, using prespecified levels of evidence, by content experts and methodological experts. VALUES: A high value was placed on the avoidance of cardiovascular morbidity and mortality. BENEFITS, HARMS, AND COSTS: Various lifestyle manoeuvres and antihypertensive agents reduce the blood pressure of patients with sustained hypertension. In certain settings, and for specific classes of drugs, blood pressure lowering has been associated with reduced cardiovascular morbidity and/or mortality. RECOMMENDATIONS: The present document contains detailed recommendations pertaining to all aspects of the therapy of patients with hypertension, including lifestyle modifications proven to lower blood pressure, treatment thresholds, target blood pressures, choice of agents in various settings and strategies to enhance adherence. Lower thresholds for blood pressure treatment are advocated for people with other cardiovascular risk factors or established hypertensive target organ damage. Implicit in the recommendations for therapy is the principle that treatment should be individualized for each patient and the choice of agent should be dictated by coexistent conditions. For the treatment of uncomplicated essential hypertension, thiazides, beta-adrenergic antagonists, angiotensin-converting enzyme inhibitors or calcium channel blockers may be appropriate, depending on individual circumstances. VALIDATION: All recommendations were graded according to strength of the evidence and voted on by the Canadian Hypertension Recommendations Working Group. Only those recommendations achieving high levels of consensus are reported here. These guidelines will be updated annually.

Fodor JG, Frohlich JJ, Genest JJ, McPherson PR. · Prevention and Rehabilitation Centre, University of Ottawa Heart Institute, Ont. · CMAJ. · Pubmed #10834048 links to  free full text

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Heathcote EJ. · Division of Gastroenterology, University of Toronto, The Toronto Hospital, Toronto, Ontario, Canada. · Hepatology. · Pubmed #10733559 No free full text.

Abstract: Primary biliary cirrhosis (PBC) is a presumed autoimmune disease of the liver, which predominantly affects women once over the age of 20 years. Most cases are diagnosed when asymptomatic (60%). The antimitochondrial antibody is present in serum in most, but not in all, patients with PBC. The disease generally progresses slowly but survival is less than an age- and gender-matched general population. The symptomatic patient may have fatigue, generalized pruritus, portal hypertension, osteoporosis, skin xanthomata, fat soluble vitamin deficiencies, and/or recurrent asymptomatic urinary tract infections. Many nonhepatic autoimmune diseases are found in association with PBC and may prompt initial presentation. To date, immunosuppressive therapy has not been shown to prolong survival in PBC. The hydrophilic bile acid, ursodeoxycholic acid (UDCA), has been shown when given in a dose of 13 to 15 mg/kg daily for up to 4 years to delay the time to liver transplantation or death. This therapy also causes a significant improvement of all the biochemical markers of cholestasis but has no beneficial effects on any of the symptoms or associated disorders. Treatment with UDCA does not obviate the need for liver transplantation. Therapies to prevent complications arising from malabsorption, portal hypertension, and/or osteoporosis are required as well. Good control of pruritus can be achieved in most patients. PBC is diagnosed with increasing frequency, but the agent(s) responsible for this slowly progressive destruction of the interlobular bile ducts remains elusive and hence a specific therapy remains unavailable.

Yusuf S, Lonn E, Bosch J. · Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, ON, Canada. · Lancet. · Pubmed #19345816 No free full text.

This publication has no abstract.

Alwaili K, Alrasadi K, Awan Z, Genest J. · Cardiovascular Research Laboratories, McGill University Health Center Research Institute, McGill University, Montreal, Quebec, Canada. · Curr Opin Endocrinol Diabetes Obes. · Pubmed #19306526 No free full text.

Abstract: PURPOSE OF REVIEW: Disorders of lipoprotein metabolism are frequently encountered in clinical practice. Although the severe genetic hyperlipidemias are relatively infrequent, prompt recognition and treatment can prevent complications, such as atherosclerosis and pancreatitis. The secondary dyslipidemias, due to medication or other metabolic disorders (hypothyroidism, renal or hepatic diseases), must be identified and treated. With the growing epidemic of obesity, dyslipidemias are a component of the metabolic syndrome. RECENT FINDINGS: The stratification of cardiovascular risk now includes family history and biomarkers of inflammation, especially high-sensitivity C-reactive protein, which enables sound clinical decision making. Lifelong hypercholesterolemia is strongly associated with increasing risk of atherosclerosis and coronary heart disease death, but the decision to treat pharmacologically depends on the absolute cardiovascular risk over the next 10 years. Clinical trial data support intensive treatment of patients at high cardiovascular risk or for the secondary prevention of recurrent coronary heart disease. The recently published JUPITER trial shows that patients with an elevated C-reactive protein benefit from treatment with a statin (rosuvastatin 20 mg) for primary prevention. SUMMARY: The current guidelines for the prevention of coronary artery disease will continue to focus on the determination of global risk, with intensive treatment aimed at the high-risk group. Family history and high-sensitivity C-reactive protein provide additional risk stratification.

Lanktree M, Hegele RA. · Vascular Biology Group, Robarts Research Institute, and Departments of Medicine & Biochemistry, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ont., Canada. · Cytogenet Genome Res. · Pubmed #19287152 No free full text.

Abstract: Despite successes in identifying genetic contributors to common metabolic phenotypes, only part of the heritable component of these traits has thus far been explained. Copy number variation (CNV) is likely to be responsible for some of the unexplained variation. As observed with single nucleotide changes, it is probable that both rare and common CNVs will contribute to susceptibility to metabolic disease. For instance, CNVs in the LDLR gene underlie a substantial portion of disease in patients with heterozygous familial hypercholesterolemia. As well, a common CNV in LPA encoding apolipoprotein(a) is the primary determinant of plasma lipoprotein(a) concentrations, a risk factor for atherosclerosis. Recent efforts to map CNVs in control populations have defined their size, frequency and distribution. Many of the identified CNVs overlap genes with important functions in metabolic pathways. The overlap of CNVs that were found in control datasets with functional candidate genes or genes with previous evidence of association with metabolic syndrome presents an important subset for future CNV association studies. Finally, we describe an approach to search for CNVs in a rare high-penetrance metabolic disorder, namely lipodystrophy. As methods to identify CNVs increase in precision and accuracy, the prospect of identifying their role in both rare Mendelian and common complex metabolic phenotypes will become a reality.

Jones PJ, AbuMweis SS. · Richardson Centre for Functional Foods and Nutraceuticals, University of Manitoba, Smartpark, Winnipeg, Manitoba, Canada. · Curr Opin Clin Nutr Metab Care. · Pubmed #19209468 No free full text.

Abstract: PURPOSE OF REVIEW: To examine experimental evidence that has examined association of phytosterols and the reduction of the risk of cardiovascular disease and cancer. RECENT FINDINGS: Phytosterols exist as naturally occurring plant sterols that are present in the nonsaponifiable fraction of plant oils. Phytosterols are plant components that have a chemical structure similar to cholesterol except for the addition of an extra methyl or ethyl group; however, phytosterol absorption in humans is considerably less than that of cholesterol. In fact, phytosterols reduce cholesterol absorption, although the exact mechanism is not known, and thus reduce circulating levels of cholesterol. The efficacy of phytosterols as cholesterol-lowering agents have been shown when incorporated into fat spreads as well as other food matrices. In addition, phytosterols have been combined with other beneficial dietary components including fish and olive oils, psyllium and beta-glucan to enhance their effect on risk factors of cardiovascular disease. Phytosterols appear not only to play an important role in the regulation of cardiovascular disease but also to exhibit anticancer properties. A side effect associated with the consumption of phytosterols is that they reduce the blood levels of carotenoid. Nevertheless, it has been suggested that compensation for this impact on serum carotenoid levels can occur either by increasing the intake of carotenoid-rich foods or by taking supplements containing these carotenoids. SUMMARY: Dietary phytosterols appear to play an important role in the regulation of serum cholesterol and to exhibit anticancer properties.

Rideout TC, Harding SV, Jones PJ, Fan MZ. · Richardson Centre for Functional Foods and Nutraceuticals, University of Manitoba, Winnipeg, Manitoba, Canada. · Vasc Health Risk Manag. · Pubmed #19183750 links to  free full text

Abstract: The hypocholesterolemic effects associated with soluble fiber consumption are clear from animal model and human clinical investigations. Moreover, the modulation of whole-body cholesterol metabolism in response to dietary fiber consumption, including intestinal cholesterol absorption and fecal sterol and bile acid loss, has been the subject of many published reports. However, our understanding of how dietary fibers regulate molecular events at the gene/protein level and alter cellular cholesterol metabolism is limited. The modern emphasis on molecular nutrition and rapid progress in 'high-dimensional' biological techniques will permit further explorations of the role of genetic polymorphisms in determining the variable interindividual responses to soluble fibers. Furthermore, with traditional molecular biology tools and the application of 'omic' technology, specific insight into how fibers modulate the expression of genes and proteins that regulate intestinal cholesterol absorption and alter hepatic sterol balance will be gained. Detailed knowledge of the molecular mechanisms by which soluble fibers reduce plasma cholesterol concentrations is paramount to developing novel fiber-based "cocktails" that target specific metabolic pathways to gain maximal cholesterol reductions.

Hegele RA. · Robarts Research Institute and Schulich School of Medicine and Dentistry, University of Western Ontario, 406-100 Perth Drive, London, Ontario, Canada N6A 5K8. · Nat Rev Genet. · Pubmed #19139765 No free full text.

Abstract: Susceptibility to the growing global public health problem of cardiovascular disease is associated with levels of plasma lipids and lipoproteins. Several experimental strategies have helped us to clarify the genetic architecture of these complex traits, including classical studies of monogenic dyslipidaemias, resequencing, phenomic analysis and, more recently, genome-wide association studies and analysis of metabolic networks. The genetic basis of plasma lipoprotein levels can now be modelled as a mosaic of contributions from multiple DNA sequence variants, both rare and common, with varying effect sizes. In addition to filling gaps in our understanding of plasma lipoprotein metabolism, the recent genetic advances will improve our ability to classify, diagnose and treat dyslipidaemias.

Poirier P. · Faculté de pharmacie de l'Université Laval, Institut universitaire de cardiologie et de pneumologie, Hôpital Laval, 2725, chemin Sainte-Foy, Sainte-Foy, Québec, G1V 4G5 Canada. · Med Sci (Paris). · Pubmed #19116122 No free full text.

This publication has no abstract.

Do R, Kiss RS, Gaudet D, Engert JC. · Department of Human Genetics, McGill University, Montreal, Quebec, Canada. · Clin Genet. · Pubmed #19054015 No free full text.

Abstract: High levels of plasma low-density lipoprotein cholesterol (LDL-C) are a significant risk factor for heart disease. Statins (3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitors) have been extensively used to treat high-plasma LDL-C levels and are effective in preventing heart disease. However, statins can be associated with adverse side effects in some patients and do not work effectively in others. As an alternative to statins, the development of cholesterol-lowering agents that directly inhibit squalene synthase have shown promise. Clinical studies have shown that squalene synthase inhibitors are effective in lowering plasma levels of total cholesterol and LDL-C. Squalene synthase plays an important role in the cholesterol biosynthesis pathway as it is responsible for the flow of metabolites into either the sterol or the non-sterol branches of the pathway. In addition, variants of the squalene synthase gene appear to modulate plasma cholesterol levels in human populations and therefore may be linked to cardiovascular disease. In this review, we examine squalene synthase and the gene that codes for it (farnesyldiphosphate farnesyltransferase 1). In particular, we investigate their role in the regulation of cellular and plasma cholesterol levels, including data that suggest that squalene synthase may be involved in the etiology of hypercholesterolemia.

Hudon C, Fortin M, Soubhi H. · Department of Family Medicine, University of Sherbrooke in Quebec, Canada. · Can Fam Physician. · Pubmed #18697975 links to  free full text

Abstract: OBJECTIVE: To provide a summary of evidence on the effectiveness of interventions to promote physical activity among patients affected by at least 1 chronic disease. The interventions studied were each targeted at a single risk factor.DATA SOURCES: MEDLINE, CINAHL, and EMBASE were searched from 1966 to 2006 using 2 sets of search terms. First we searched using physical activity or physical fitness or exercise and health care or primary care or primary health care or family practice or medical office or physician's office and health promotion or health education or counselling. Then we used physical activity or exercise and diabetes or hyperlipidemia or hypertension or obesity or cardiovascular disease or pulmonary disease or risk factor or comorbidity and health promotion or health education or counselling or prescription. STUDY SELECTION: We chose randomized controlled trials or trials with a controlled quasi-experimental design that evaluated single risk factor interventions to promote physical activity among adult patients in primary care settings who were affected by at least 1 chronic disease, that reported participation in physical activity as a primary outcome, and that were published in English or French. SYNTHESIS: Of the 4858 articles found, 62 were assessed, and 3 were selected. Two studies concluded that the interventions evaluated had no effect on level of physical activity. The other reported a positive short-term effect with use of an intensive intervention that was based on the theory of planned behaviour and integrated nurses into the general practitioner counseling process. CONCLUSION: There is insufficient evidence to assess the effectiveness of single risk factor interventions to promote physical activity among patients affected by at least 1 chronic disease in primary care settings. Of 3 studies, only 1 reported a short-term positive effect.

Machado M, Nassor N, Bajcar JM, Guzzo GC, Einarson TR. · Toronto Health Economics and Technology Assessment Collaborative, University of Toronto, Toronto, Ontario, Canada. · Ann Pharmacother. · Pubmed #18682540 No free full text.

Abstract: BACKGROUND: Hyperlipidemia increases the risk of cardiovascular diseases, and control is pivotal for preventing disease complications. Multidisciplinary interventions, including those performed by pharmacists, are important for improving patients' outcomes. OBJECTIVE: To quantify the impact of pharmacist interventions in enhancing patients' outcomes. METHODS: Two reviewers searched International Pharmaceutical Abstracts, MEDLINE, EMBASE, The Cochrane Central Register of Controlled Trials, 3rd Quarter, and Cumulative Index to Nursing and Allied Health Literature (all from inception to July 2007) for pharmacist interventions in hyperlipidemia. Quality was assessed using the Downs-Black scale. Data extracted included the number of patients enrolled; study characteristics; intervention type; and pre- and postintervention measures for low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides, total cholesterol, adherence, and quality of life. A random effects meta-analysis combined data. Heterogeneity of effects was tested using chi(2) analysis. Publication bias was assessed using funnel plots and the Begg-Mazumdar statistic. RESULTS: Forty-eight studies were found; 23 met inclusion criteria. Study settings included medical clinic/center (n = 12), community pharmacy (n = 8), hospital (n = 2), and patient homes (n = 1). Article quality was good (71% +/- 7.0%). Patient education (78%) and medication management (74%) were the most common interventions. Total cholesterol was significantly reduced from baseline (mean +/- SD; 34.3 +/- 10.3 mg/dL; p < 0.001) and above that for controls (22.0 +/- 10.4 mg/dL; p = 0.034). LDL-C was reduced significantly from baseline (32.6 +/- 11.3 mg/dL; p = 0.004), but not significantly more than controls (17.5 +/- 10.9 mg/dL; p = 0.109). A clinically relevant but not statistically significant reduction in triglycerides was found. No impact on HDL-C levels was found. Patients' adherence to pharmacotherapeutic regimens and quality of life were considered possibly not sensitive and possibly sensitive to pharmacist interventions, respectively. CONCLUSIONS: Total cholesterol is sensitive to pharmacist interventions, while LDL-C and triglyceride levels are possibly sensitive to those interventions. Further research is required for these outcomes.

Rosenberg H, Allard D. · Health and Society Program, Division of Social Science, York University, Toronto, Ontario, Canada. · Scand Cardiovasc J. · Pubmed #18609063 No free full text.

Abstract: This paper is based on a longer report on the benefits, safety and modalities of information representation with regard to women and statin use, situated within the historical context of Women's Health Movement which has advocated for unbiased, appropriate medical research and prescribing for women based on the goals of full-disclosure, informed consent, evidence-based medicine and gender-based analysis. The evidence base for prescribing statins for women, especially for primary prevention is weak, yet Canadian data suggest that half of all prescriptions are for women. Safety meta-analyses do not disaggregate for women; do not consider female vulnerability to statin induced muscle problems, and women-centred concerns such as breast-cancer, miscarriage or birth defects are under-researched. Many trials have not published their non-cardiac serious adverse event data. These factors suggest that the standards of full-disclosure, informed consent, evidence-based prescribing and gender-based analysis are not being met and women should proceed with caution.

Rudkowska I, Jones PJ. · School of Dietetics and Human Nutrition, Faculty of Agricultural and Environmental Sciences, McGill University, Ste-Anne-de-Bellevue, Quebec, Canada. · Nutr Rev. · Pubmed #18522623 No free full text.

Abstract: ATP-binding cassette (ABC) transporters function in the homeostasis of lipids. Dysfunction of ABC transporters is frequently associated with disease. This review examines links between polymorphisms of ABC G5 (ABCG5) and G8 (ABCG8) transporter genes to hypercholesterolemia and to gallstone disease risk. Various polymorphisms (A632V, T400K, D19H, M429V, and C54Y) in the ABCG8 and ABCG5 (Q604E) gene have been found to be associated with several facets of cholesterol metabolism, including baseline cholesterol level, cholesterol kinetics, individual responsiveness of plasma cholesterol to dietary and pharmaceutical interventions for hypercholesterolemia, and increased risk of gallstones. Clearly, the ABCG5 and ABCG8 genes play an important role in cholesterol homeostasis. However, more research is needed to establish how specific polymorphisms of these genes confer to higher risk of these diseases.

Joy TR, Hegele RA. · Blackburn Cardiovascular Genetics Laboratory, The Robarts Research Institute, in London, ON, Canada. · Nat Clin Pract Cardiovasc Med. · Pubmed #18506153 No free full text.

Abstract: This article sets out the clinical context of the research presented by Samaha et al. in an accompanying article in this issue. Hyperlipidemia is a common and important risk factor for cardiovascular disease. Current lipid-lowering therapies, particularly statins, lead to substantial decreases in cardiovascular disease morbidity and mortality, but use has been limited by safety or efficacy issues. The way has, therefore, been paved for the pharmaceutical development and clinical investigation of new lipid-lowering therapies. The clinical trial by Samaha et al. examines the safety and efficacy of microsomal triglyceride transfer protein inhibition for lowering lipids. Joy and Hegele explore the difficulties of translating microsomal triglyceride transfer protein inhibition into clinical practice because of the trade-off between efficacy and potential adverse effects. They also stress the need for outcome studies, rather than biochemical or surrogate studies, as the final arbiter for the clinical use of this new treatment.

Xiao CW. · Nutrition Research Division, Food Directorate, Health Products and Food Branch, Health Canada, 2203E Banting Research Centre, Ottawa, Canada. · J Nutr. · Pubmed #18492864 links to  free full text

Abstract: Epidemiological investigations suggest that soy consumption may be associated with a lower incidence of certain chronic diseases. Clinical studies also show that ingestion of soy proteins reduces the risk factors for cardiovascular disease. This led to the approval of the food-labeling health claim for soy proteins in the prevention of coronary heart disease by the U.S. FDA in 1999. Similar health petitions for soy proteins have also been approved thereafter in the United Kingdom, Brazil, South Africa, the Philippines, Indonesia, Korea, and Malaysia. However, the purported health benefits are quite variable in different studies. The Nutrition Committee of the American Heart Association has assessed 22 randomized trials conducted since 1999 and found that isolated soy protein with isoflavones (ISF) slightly decreased LDL cholesterol but had no effect on HDL cholesterol, triglycerides, lipoprotein(a), or blood pressure. The other effects of soy consumption were not evident. Although the contributing factors to these discrepancies are not fully understood, the source of soybeans and processing procedures of the protein or ISF are believed to be important because of their effects on the content and intactness of certain bioactive protein subunits. Some studies have documented potential safety concerns on increased consumption of soy products. Impacts of soy products on thyroid and reproductive functions as well as on certain types of carcinogenesis require further study in this context. Overall, existing data are inconsistent or inadequate in supporting most of the suggested health benefits of consuming soy protein or ISF.

Roberts R. · University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, Ontario, K1Y 4W7, Canada. · Curr Atheroscler Rep. · Pubmed #18489845 No free full text.

Abstract: Common multigene disorders account for 80% of deaths in the world and all have significant genetic predisposition. Coronary artery disease and myocardial infarction (MI) account for more than 40% of these deaths. The genetic component is due to multiple genes, each contributing only minimally to the phenotype. Linkage analysis, which has been successful in identifying rare disorders that cause MI, is not sensitive for multigene disorders. The recent candidate case-control approach has been equally unsuccessful. Multigene disorders require genome-wide association studies involving genotyping hundreds of thousands of DNA markers in thousands of individuals with replication in independent populations. Platforms with 500,000 and 1 million single nucleotide polymorphisms provide the necessary high-throughput genotyping for genome-wide association. The first confirmed common locus, 9p21, is independent of conventional risk factors. Identifying the 9p21 gene will elucidate novel mechanisms responsible for MI. Comprehensive prevention of MI based on individual genetic variants (personalized medicine) is expected in the next decade.

Moride Y, Hegele RA, Langer A, McPherson R, Miller DB, Rinfret S. · Faculty of Pharmacy, Université de Montreal, Montréal, Quebec. · Can J Cardiol. · Pubmed #18401470 links to  free full text

Abstract: Peer-reviewed, evidence-based recommendations for statin use in primary prevention of cardiovascular events are limited. A narrative review of published randomized controlled trials and meta-analyses was conducted to critically appraise the benefits and risks of statins in primary prevention. Statins effectively reduce plasma concentrations of low-density lipoprotein cholesterol, and reduce the risk of cardiovascular events and death. The greatest benefits are observed in high-risk subjects, such as patients with diabetes or hypertension. Serious cardiovascular events should not be included among serious adverse events because they are efficacy outcomes and are dependent on the baseline risk of patients. Rates of specific serious adverse events, such as cancer and rhabdomyolysis, seem to be similar between the statin and control arms of the clinical trials examined. Thus, the benefits of statins in primary prevention outweigh the risks, particularly among high-risk patients. However, the benefit-risk ratio would likely be optimized through interventions designed to increase persistence and adherence in a real-life setting.

Jenkins DJ, Josse AR, Wong JM, Nguyen TH, Kendall CW. · Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, 150 College Street, Room 340,Toronto, Ontario, M5S 3E2, Canada. · Curr Atheroscler Rep. · Pubmed #18377791 No free full text.

Abstract: Prompted by current dietary recommendations for the control of serum cholesterol to new targets to reduce the risk of coronary heart disease (CHD), and by the CHD risk reduction claims made for certain foods or food components, studies are now being undertaken using combinations of cholesterol-lowering foods in one diet (eg, a dietary portfolio) rather than single foods to achieve more effective dietary control of serum cholesterol. This approach has increased the potential relevance of dietary therapy and may yield nutrition strategies that bridge the gap between what is regarded as a good diet and drug therapy.

Patterson C, Feightner JW, Garcia A, Hsiung GY, MacKnight C, Sadovnick AD. · Division of Geriatric Medicine, McMaster University, Hamilton, Ont. · CMAJ. · Pubmed #18299540 links to  free full text

Abstract: BACKGROUND: In addition to nonmodifiable genetic risk factors, potentially modifiable factors such as hypertension, hyperlipidemia and environmental exposures have been identified as risk factors for Alzheimer disease. In this article, we provide physicians with practical guidance on risk assessment and primary prevention of Alzheimer disease based on recommendations from the Third Canadian Consensus Conference on the Diagnosis and Treatment of Dementia, held in March 2006. METHODS: We developed evidence-based guidelines using systematic literature searches, with specific criteria for study selection and quality assessment, and a clear and transparent decision-making process. We selected studies published from January 1996 to December 2005 that met the following criteria: dementia (all-cause, Alzheimer disease or vascular dementia) as the outcome; longitudinal cohort study; study population broadly reflective of Canadian demographics; and genetic risk factors and general risk factors (e.g., hypertension, education, occupation and chemical exposure) identified. We graded the strength of evidence using the criteria of the Canadian Task Force on Preventive Health Care. RESULTS: Of 3424 articles on potentially modifiable risk factors for dementia, 1719 met our inclusion criteria; 60 were deemed to be of good or fair quality. Of 1721 articles on genetic risk factors, 62 that met our inclusion criteria were deemed to be of good or fair quality. On the basis of evidence from these articles, we made recommendations for the risk assessment and primary prevention of Alzheimer disease. For the primary prevention of Alzheimer's disease, there is good evidence for controlling vascular risk factors, especially hypertension (grade A), and weak or insufficient evidence for manipulation of lifestyle factors and prescribing of medications (grade C). There is good evidence to avoid estrogens and high-dose (> 400 IU/d) of vitamin E for this purpose (grade E). Genetic counselling and testing may be offered to at-risk individuals with an apparent autosomal dominant inheritance (grade B). Screening for the apolipoprotein E genotype in asymptomatic individuals in the general population is not recommended (grade E). INTERPRETATION: Despite the personal and societal burden of dementia, our understanding of genetic predisposition to dementias and the contribution of other risk factors remains limited. More importantly, there are few data to explain the overall risks and benefits of prevention strategies or their impact of risk modification.

Joy T, Cao H, Black G, Malik R, Charlton-Menys V, Hegele RA, Durrington PN. · Department of Vascular Biology and Medicine, Robarts Research Institute and Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada. · Orphanet J Rare Dis. · Pubmed #18154657 links to  free full text

Abstract: BACKGROUND: Alstrom syndrome (AS) is a rare autosomal recessive disease characterized by multiorgan dysfunction. The key features are childhood obesity, blindness due to congenital retinal dystrophy, and sensorineural hearing loss. Associated endocrinologic features include hyperinsulinemia, early-onset type 2 diabetes, and hypertriglyceridemia. Thus, AS shares several features with the common metabolic syndrome, namely obesity, hyperinsulinemia, and hypertriglyceridemia. Mutations in the ALMS1 gene have been found to be causative for AS with a total of 79 disease-causing mutations having been described. CASE PRESENTATION: We describe the case of a 27-year old female from an English (Caucasian) kindred. She had been initially referred for hypertriglyceridemia, but demonstrated other features suggestive of AS, including blindness, obesity, type 2 diabetes, renal dysfunction, and hypertension. DNA analysis revealed that she is a compound heterozygote with two novel mutations in the ALMS1 gene - H3882Y and V424I. Examination of her family revealed that her phenotypically unaffected mother and younger sister also had heterozygous mutations in the ALMS1 gene. In addition to presenting these novel molecular findings for AS, we review the clinical and genetic features of AS in the context of our case. CONCLUSION: Two novel mutations in the ALMS1 gene causative for AS have been reported here, thereby increasing the number of reported mutations to 81 and providing a wider basis for mutational screening among affected individuals.

Rahalkar AR, Hegele RA. · Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ont., Canada. · Mol Genet Metab. · Pubmed #18023224 No free full text.

Abstract: Monogenic disorders that cause abnormal levels of plasma cholesterol and triglycerides have received much attention due to their role in metabolic dysfunction and cardiovascular disease. While these disorders often present clinically during adulthood, some present most commonly in the pediatric population and can have serious consequences if misdiagnosed or untreated. This review provides an overview of monogenic lipid disorders that present with unusually high or low levels of plasma cholesterol and/or triglycerides during infancy, childhood and adolescence. Biochemical and genetic findings, clinical presentation and treatment options are discussed with an emphasis upon recent advances in our understanding and management of these monogenic disorders.