Hyperlipidemias: Canada

Lemieux I, Poirier P, Bergeron J, Alméras N, Lamarche B, Cantin B, Dagenais GR, Després JP. · Hôpital Laval Research Centre, Quebec. · Can J Cardiol. · Pubmed #17932584 No free full text.

Abstract: The worldwide increase in the prevalence and incidence of type 2 diabetes represents a tremendous challenge for the Canadian health care system, especially if we consider that this phenomenon may largely be explained by the epidemic of obesity. However, despite the well-recognized increased morbidity and mortality associated with an elevated body weight, there is now more and more evidence highlighting the importance of intra-abdominal adipose tissue (visceral adipose tissue) as the fat depot conveying the greatest risk of metabolic complications. In this regard, body fat distribution, especially visceral adipose tissue accumulation, has been found to be a key correlate of a cluster of diabetogenic, atherogenic, prothrombotic and inflammatory metabolic abnormalities now often referred to as the metabolic syndrome. This dysmetabolic profile is predictive of a substantially increased risk of coronary artery disease (CAD) even in the absence of hyperglycemia, elevated low-density lipoprotein cholesterol or hypertension. For instance, some features of the metabolic syndrome (hyperinsulinemia, elevated apolipoprotein B and small low-density lipoprotein particles--the so-called atherogenic metabolic triad) have been associated with a more than 20-fold increase in the risk of ischemic heart disease in middle-aged men enrolled in the Quebec Cardiovascular Study. This cluster of metabolic complications has also been found to be predictive of a substantially increased risk of CAD beyond the presence of traditional risk factors. These results emphasize the importance of taking into account in daily clinical practice the presence of metabolic complications associated with abdominal obesity together with traditional risk factors to properly evaluate the cardiovascular risk profile of patients. From a risk assessment standpoint, on the basis of additional work conducted by several groups, there is now evidence that the simultaneous presence of an elevated waist circumference and fasting triglyceride levels (a condition that has been described as hypertriglyceridemic waist) may represent a relevant first-step approach to identify a subgroup of individuals at higher risk of being carriers of the features of the metabolic syndrome. Moreover, a moderate weight loss in initially abdominally obese patients is associated with a selective mobilization of visceral adipose tissue, leading to improvements in the metabolic risk profile predictive of a reduced risk of CAD and type 2 diabetes. In conclusion, hypertriglyceridemic waist as a marker of visceral obesity and related metabolic abnormalities is a useful and practical clinical phenotype to screen persons at risk for CAD and type 2 diabetes.

Mangat R, Su J, Scott PG, Russell JC, Vine DF, Proctor SD. · Metabolic and Cardiovascular Diseases Laboratory, Alberta Institute for Human Nutrition, University of Alberta, Edmonton, AB, Canada, T6G 2PS. · Biochem Soc Trans. · Pubmed #17511632 No free full text.

Abstract: Postprandial (PP) lipaemia is a significant contributor to the development of dyslipidaemia and cardiovascular disease (CVD). It is also evident that PP lipaemia is prevalent during conditions of obesity and insulin resistance (IR) and may contribute to increased progression of CVD. Our group has assessed the potential of the obese JCR:LA-cp rat as a model of PP lipaemia in order to explore CM (chylomicron) metabolism during the onset and development of IR in the metabolic syndrome. Studies confirm that both fasting plasma and PP apoB48 (apolipoprotein B48) area under the curve are significantly elevated in the obese JCR:LA-cp phenotype as compared with lean controls. Mechanistic studies have also shown that the concentration of lymphatic CM apoB48 and CM size are significantly increased in this model. Furthermore, PP dyslipidaemia in the obese rat can be improved acutely with supplementation of n-3 polyunsaturated fatty acids. Using a different approach, we have subsequently hypothesized that the vascular remodelling that accompanies IR may explain accelerated entrapment of apoB48-containing particles. Small leucine-rich proteoglycans (including biglycan and decorin) have been observed to co-localize with apoB in human tissue. However, the potential impact of IR on vascular remodelling, particularly in the presence of obesity, remains unclear. Preliminary observations from the JCR:LA-cp model indicate that biglycan protein core content increases with age and is exacerbated by IR, suggestive of pro-atherogenic remodelling. The focus of this review is to contribute to the perspective of PP lipaemia in CVD risk associated with the metabolic syndrome through the use of animal models.

Daskalopoulou SS, Daskalopoulos ME, Mikhailidis DP, Liapis CD. · Department of Medicine, Division of Clinical Epidemiology, McGill University, Montreal, Quebec, Canada. · Curr Drug Targets. · Pubmed #17430127 No free full text.

Abstract: Peripheral arterial disease (PAD) is a common disorder usually associated with silent or symptomatic arterial disease elsewhere in the circulation and a "cluster" of cardiovascular risk factors (e.g. smoking, dyslipidemia, hypertension, and insulin resistance/diabetes mellitus). The medical management of PAD should focus on both the relief of symptoms and prevention of secondary cardiovascular complications. This approach must include smoking cessation, optimal cholesterol levels, blood pressure and glycemic control as well as prescribing antiplatelet therapy. This review focuses on the evidence supporting the use of lipid-lowering drugs in PAD. Several trials indicate that getting low density lipoprotein-cholesterol levels to target (<2.6 mmol/l; 100 mg/dl), or even lower, is associated with improvement of symptoms and a reduction in vascular events in patients with PAD.

Hegele RA. · Blackburn Cardiovascular Genetics Laboratory, Robarts Research Institute, Schulich School of Medicine and Dentistry, University of Western Ontario, 406-100 Perth Drive, London, ON N6A 5K8, Canada. · Genome. · Pubmed #17426749 No free full text.

Abstract: Much of the recent progress in treating patients with heart disease due to narrowed coronary arteries has resulted from studying disease evolution in patients with rare monogenic forms of disease. For instance, autosomal dominant familial hypercholesterolemia (FH, MIM (Mendelian Inheritance in Man) 143890) typically results from heterozygous mutations in LDLR encoding the low-density lipoprotein (LDL) receptor. Deficient LDLR activity results in elevated circulating LDL cholesterol, which accumulates within blood vessel walls, forming arterial plaques that can grow and eventually occlude the arterial lumen. Heterozygous LDLR mutations are usually detected using exon-by-exon sequence analysis (EBESA) of genomic DNA, a technology that has identified approximately 50 mutations in heterozygous FH (HeFH) subjects in Ontario. However, approximately 35% of Ontario HeFH patients had no EBESA-identified LDLR mutation. The diagnostic gap relates both to the genetic heterogeneity of FH and also to inadequate sensitivity of EBESA to detect certain mutation types, such as large deletions or insertions in LDLR. By means of a dedicated method to detect copy number variations (CNVs), additional heterozygous mutations in LDLR ranging from approximately 500 to >15 000 bases were uncovered, accounting for most of the remainder of Ontario HeFH patients. The appreciation of the key role of genomic CNVs in disease coincides with recent genome-wide mapping studies demonstrating that CNVs are common in apparently healthy people. CNVs thus represent a new level of genomic variation that is both an important mechanism of monogenic disease and a contributor to genomic variation in the general population; as well, it may have implications for evolution, biology, and possibly susceptibility to common complex diseases.

Yuan G, Al-Shali KZ, Hegele RA. · Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ont. · CMAJ. · Pubmed #17420495 links to  free full text

Abstract: Elevated plasma triglyceride concentration is a common biochemical finding, but the evidence for the benefit of treating this lipid disturbance remains less robust than that for treating elevated low-density lipoprotein-cholesterol. Part of the difficulty in the provision of specific recommendations has been the frequent coexistence of elevated triglycerides with other conditions that affect cardiovascular disease risk, such as depressed high-density lipoprotein-cholesterol, obesity, metabolic syndrome, proinflammatory and prothrombotic biomarkers, and type 2 diabetes. Recent investigations of outcomes of cardiovascular disease when medications are used to reduce triglyceride levels suggest that, although a net benefit probably exists, both relative and absolute risk reductions seem underwhelming when compared with the benefit of reducing low-density lipoprotein-cholesterol levels with treatment. However, the totality of evidence suggests that elevated triglyceride levels likely contribute independently to increased risk of cardiovascular disease, although there is no consensus about appropriate target levels. Furthermore, severe hypertriglyceridemia is associated with an increased risk of acute pancreatitis, irrespective of its effect on risk of cardiovascular disease. We review the causes and classification of elevated triglyceride levels, the clinical manifestations of primary hypertriglyceridemia and the management of patients with elevated triglyceride levels.

Leiter LA. · Division of Endocrinology and Metabolism, St Michael's Hospital, Toronto, Ontario, Canada. · J Fam Pract. · Pubmed #17403328 No free full text.

This publication has no abstract.

Pollex RL, Hegele RA. · Robarts Research Institute, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada. · Curr Opin Lipidol. · Pubmed #17353666 No free full text.

Abstract: PURPOSE OF REVIEW: This review examines the role of copy number variation in the human genome as a newly recognized determinant of lipoprotein and metabolic phenotypes. RECENT FINDINGS: Much of the recent progress defining the molecular basis of lipoprotein disorders has been the result of studying genomic DNA at the single nucleotide level, for instance with nucleotide sequence analysis or genotyping to detect single nucleotide polymorphisms. Focus on single nucleotides, however, fails to capture the complete spectrum of potential genetic variability. Recent genome-wide mapping studies have demonstrated the surprising ubiquity of large-scale copy number variations in apparently healthy people, adding to the complexity of the 'normal' genome, but also emphasizing this form of genetic variation as a potential disease mechanism. The application of this understanding to the genetics of lipoprotein disorders has been rapid. For instance, the use of novel techniques to detect copy number variations, such as multiplex ligation-dependent probe amplification, has revealed many additional causative mutations in the low-density lipoprotein receptor gene in patients with familial hypercholesterolemia. SUMMARY: Copy number variations thus represent a new level of genomic variation that is both an important mechanism of monogenic lipoprotein disorders and a potential contributor to common complex lipoprotein and metabolic phenotypes in the general population.

Rashid S. · Department of Cardiology, McGill University, Montreal, Quebec. · Can J Cardiol. · Pubmed #17347688 links to  free full text

Abstract: Cardiovascular disease (CVD) presents an enormous and growing burden on the Canadian health care system. Elevated serum low-density lipoprotein cholesterol levels are an established, major risk factor in the development of premature CVD. There is strong evidence that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, or statins, significantly lower both low-density lipoprotein cholesterol levels and CVD risk. However, there is currently a treatment gap, in that a large segment of the population who should be receiving statins due to elevated serum cholesterol levels are not. Individuals at moderate risk of developing CVD represent one large population segment that is currently being undertreated. This group may be a candidate for receiving over-the-counter (OTC) or behind-the-counter (BTC) statins, which may be a suitable primary prevention strategy. Nonetheless, it must be noted that hypercholesterolemia is a complex, chronic condition that must be carefully managed and requires close consultation with a health care practitioner. The advantages and disadvantages of OTC or BTC statin usage must therefore be carefully weighed before any potential introduction of OTC or BTC statins in Canada.

Paglialunga S, Cianflone K. · McGill University, Department of Biochemistry, Montreal, QC H3G 1Y6, Canada. · Appl Physiol Nutr Metab. · Pubmed #17332785 No free full text.

Abstract: People spend a large percentage of their waking hours in the postprandial state. Postprandial lipemia is associated with disruptions in lipoprotein metabolism and inflammatory factors, cardiovascular disease, MetS, and diabetes. Commonly, the dietary sources of fat exceed the actual needs and the tissues are faced with the excess, with accumulation of chylomicrons and remnant particles. This review will summarize recent findings in postprandial lipemia research with a focus on human studies. The effects of dietary factors and other meal components on postprandial lipemia leads to the following question: do we need a standardized oral lipid tolerance test (OLTT)? An overview of recent findings on FABP2, MTP, LPL, apoAV, and ASP and the effects of body habitus (sex influence and body size), as well as exercise and weight loss, on postprandial lipemia will be summarized.

Gan SI, Edwards AL, Symonds CJ, Beck PL. · Division of Gastroenterology and Endocrinology, Foothills Hospital, University of Calgary, Calgary, Alberta, Canada. · World J Gastroenterol. · Pubmed #17131487 links to  free full text

Abstract: Hypertriglyceridemia is an established cause of pancreatitis. In a case-based approach, we present a review of hypertriglyceridemia and how it can cause pancreatitis. We outline how to investigate and manage such patients. A 35 year old man presented to the emergency department with abdominal pain and biochemical evidence of acute pancreatitis. There was no history of alcohol consumption and biliary imaging was normal. The only relevant past medical history was that of mild hyperlipidemia, treated with diet alone. Physical exam revealed epigastric tenderness, right lateral rectus palsy, lipemia retinalis, bitemporal hemianopsia and a delay in the relaxation phase of his ankle reflexes. Subsequent laboratory investigation revealed marked hypertriglyceridemia and panhypopituarism. An enhanced CT scan of the head revealed a large suprasellar mass impinging on the optic chiasm and hypothalamus. The patient was treated supportively; thyroid replacement and lipid lowering agents were started. He underwent a successful resection of a craniopharyngioma. Post-operatively, the patient did well on hormone replacement therapy. He has had no further attacks of pancreatitis. This case highlights many of the factors involved in the regulation of triglyceride metabolism. We review the common causes of hypertriglyceridemia and the proposed mechanisms resulting in pancreatitis. The incidence and management of hypertriglyceridemia-induced pancreatitis are also discussed.

Thavendiranathan P, Bagai A, Brookhart MA, Choudhry NK. · Department of Medicine, University of Toronto, Toronto, Ontario. · Arch Intern Med. · Pubmed #17130382 links to  free full text

Abstract: BACKGROUND: While the role of hydroxymethyl glutaryl coenzyme A reductase inhibitors (statins) in secondary prevention of cardiovascular (CV) events and mortality is established, their value for primary prevention is less clear. To clarify the role of statins for patients without CV disease, we performed a meta-analysis of randomized controlled trials (RCTs). METHODS: MEDLINE, EMBASE, Cochrane Collaboration, and American College of Physicians Journal Club databases were searched for RCTs published between 1966 and June 2005. We included RCTs with follow-up of 1 year or longer, more than 100 major CV events, and 80% or more of the population without CV disease. From each trial, demographic data, lipid profile, CV outcomes, mortality, and adverse outcomes were recorded. Summary relative risk (RR) ratios with 95% confidence intervals (CIs) were calculated using a random effects model. RESULTS: Seven trials with 42,848 patients were included. Ninety percent had no history of CV disease. Mean follow-up was 4.3 years. Statin therapy reduced the RR of major coronary events, major cerebrovascular events, and revascularizations by 29.2% (95% CI, 16.7%-39.8%) (P<.001), 14.4% (95% CI, 2.8%-24.6%) (P = .02), and 33.8% (95% CI, 19.6%-45.5%) (P<.001), respectively. Statins produced a nonsignificant 22.6% RR reduction in coronary heart disease mortality (95% CI, 0.56-1.08) (P = .13). No significant reduction in overall mortality (RR, 0.92 [95% CI, 0.84-1.01]) (P = .09) or increases in cancer or levels of liver enzymes or creatine kinase were observed. CONCLUSION: In patients without CV disease, statin therapy decreases the incidence of major coronary and cerebrovascular events and revascularizations but not coronary heart disease or overall mortality.

Sniderman AD, Marcovina SM. · Mike Rosenbloom Laboratory for Cardiovascular Research, Room H7.22, McGill University Health Centre, 687 Pine Avenue West, Montreal, Quebec H3A 1A1, Canada. · Clin Lab Med. · Pubmed #17110237 No free full text.

Abstract: This article reviews the evidence showing that apolipoprotein (apo) B and A-1 are superior to the conventional cholesterol indices as analytes in laboratory practice, indices of the lipoprotein-related risk for vascular disease, and measures of the adequacy of low-density lipoprotein-lowering therapy.

Caetano PA, Lam JM, Morgan SG. · Centre for Health Services and Policy Research, University of British Columbia, Vancouver, British Columbia. · Clin Ther. · Pubmed #17062314 No free full text.

Abstract: BACKGROUND: Long-term utilization of prescription drugs for chronic conditions such as hypertension and/or hypercholesterolemia is a reality for millions of individuals, yet therapies may be discontinued before they can exert their beneficial effect. Several studies have measured the mean duration of therapy (ie, persistence) using administrative health databases. However, the terminology and methodology used for measuring persistence varied across studies, making it difficult to compare persistence rates. OBJECTIVES: The objectives of this study were to identify currently used measures of persistence and to propose a standard operational definition for use in administrative database analyses of drug utilization. METHODS: MEDLINE was searched for English-language articles published between January 1997 and June 2005 that quantified the concepts of persistence, adherence, compliance, or continuity with statin or antihypertensive therapy using administrative prescription claims databases. The conceptual and operational definitions of persistence used in the identified studies were categorized and applied to prescription-refill data for a hypothetical patient to compare the durations of persistence resulting from each method. RESULTS: Thirty-one articles were identified and reviewed. Few of the studies explicitly stated the conceptual definition of persistence used. Five methods of measuring persistence were identified: anniversary models, minimum-refills models, refill-sequence models, proportion-of-days-covered models, and hybrid models. When these models were applied to data for the hypothetical patient, total persistence with drug therapy ranged from 7 days to >1 year. CONCLUSIONS: There continue to be inconsistencies in the definition of persistence and the methods by which it is measured. A standard operational definition of persistence should be 2-dimensional, quantifying not only the total duration of therapy, but also the intensity of medication-taking within this interval.

Pritchard KI, Abramson BL. · Toronto-Sunnybrook Regional Cancer Centre, Sunnybrook Health Sciences Centre, and the University of Toronto, Toronto, Ontario, Canada. · Drugs. · Pubmed #16978036 No free full text.

Abstract: Cardiovascular disease is the most frequent cause of death in North American women, and so death resulting from cardiovascular disease, rather than from malignancy, is not uncommon in breast cancer patients. This may be a consequence of the shared risk factors for developing breast cancer and cardiovascular disease, as well as the difficulty of managing cancer patients at higher risk for developing cardiovascular disease. Recently, much attention has focused on understanding the cardiovascular risk factors associated with breast cancer therapies. Tamoxifen has a lowering effect on serum lipids and is reported to decrease the risk of myocardial infarction but to increase the risk of thromboembolic events. Current data indicate that aromatase inhibitors (AIs) are not associated with an increased risk of thromboembolic or cerebrovascular events. Reports of a greater incidence of hypercholesterolaemia when AIs are compared head-to-head with tamoxifen may be a result of the intrinsic lipid-lowering effects of tamoxifen therapy and may be confounded by differences in data collection among trials. The incidence of cardiovascular events associated with AIs in large trials has been reported to be higher in trials comparing AIs with tamoxifen; comparisons within the MA.17 trial, which evaluated an AI versus placebo, did not show increases in hypercholesterolaemia or in cardiovascular events with the AI.When treating breast cancer patients, oncologists should consider the same positive lifestyle changes that are proposed to lower the risk of cardiovascular disease in patients who do not have breast cancer. Moreover, physicians should assess cardiovascular risk, and monitor and treat patients already diagnosed with or at risk for coronary heart disease, according to established guidelines.

Sigal R, Malcolm J, Arnaout A. · Clinical Epidemiology Program, Ottawa Hospital, Ottawa, Canada. · Clin Evid. · Pubmed #16973029 No free full text.

This publication has no abstract.

Cheng AY, Leiter LA. · Division of Endocrinology and Metabolism, St. Michael's Hospital, Canada. · Curr Opin Cardiol. · Pubmed #16755211 No free full text.

Abstract: PURPOSE OF REVIEW: In 2001, the Adult Treatment Panel III of the National Cholesterol Education Program issued recommendations, which were updated in 2004 to reflect knowledge from five major clinical trials completed after 2001. This review discusses the results of key clinical trials released in 2005 and their potential impact on the guidelines. RECENT FINDINGS: Three major clinical trials, one subgroup analysis, and one meta-analysis were published in 2005 that can potentially affect the existing guidelines. The Treating to New Targets and the Incremental Decrease in End Points Through Aggressive Lipid Lowering trials demonstrated the incremental benefit of more aggressive low-density cholesterol lowering in stable coronary heart disease. The Cholesterol Treatment Trialists' Collaboration meta-analysis of statin trials supported the importance of low-density lipoprotein cholesterol reduction, irrespective of initial lipid profile, in reducing cardiovascular events. A subgroup analysis of the Anglo-Scandinavian Cardiac Outcomes Trial - Lipid-Lowering Arm demonstrated statin benefits in diabetes, whereas the Fenofibrate Intervention and Event Lowering in Diabetes study failed to show overall treatment benefits with a fibrate in diabetes. SUMMARY: Lowering of low-density lipoprotein cholesterol remains central in reducing cardiovascular risk; however, the recent trials support a target of less than 2.0 mmol/l (<80 mg/dl), rather than the less than 1.8 mmol/l (70 mg/dl) suggested by the 2004 update, for all high-risk patients and not, as recommended previously, just for those with additional factors. For individuals with diabetes, recent data support the use of statin therapy, even in those at less than high risk. First-line therapy should remain statins and not fibrates.

McCrindle BW. · Division of Cardiology, Department of Pediatrics, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, Canada M5G 1X8. · Thromb Res. · Pubmed #16709475 No free full text.

Abstract: Hyperlipidemia in children has emerged as an increasingly prevalent risk factor in children, concomitant with the worldwide epidemic of obesity. Hyperlipidemia can alter vascular endothelial function and impair some of its pro-fibrinolytic and anti-thrombotic regulatory properties, as well as initiate the atherosclerotic process. There are strong links between vascular changes and hyperlipidemia in children, both from pathologic and non-invasive assessment studies. More severe lipid abnormalities in children are related to primary familial dyslipidemias. Current recommendations for screening begin with assessment of family history for cardiovascular disease or events or parental hyperlipidemia. High-risk individuals merit more intensive investigation and intervention. While fat-restricted diets have been shown to be safe in children, lipid-lowering is modest. Those with more severe lipid abnormalities may meet criteria for drug therapy, and the statin agents commonly used in adults are increasingly being used in high-risk children, with similar efficacy and safety, although long-term concerns remain.

Yuan G, Wang J, Hegele RA. · Department of Medicine, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ont. · CMAJ. · Pubmed #16606962 links to  free full text

Abstract: Heterozygous familial hypercholesterolemia (HeFH) is a monogenic disorder that affects about 1 in 500 people, with a higher prevalence in certain subpopulations such as people of Quebecois, Christian Lebanese and Dutch South Afrikaner extraction. HeFH is characterized by cholesterol deposits affecting the corneas, eyelids and extensor tendons; elevated plasma concentrations of low-density lipoprotein (LDL) cholesterol; and accelerated vascular disease, especially coronary artery disease (CAD). Although HeFH is genetically heterogeneous, it is most often caused by heterozygous mutations in the LDLR gene encoding the LDL receptor. We describe a man who was diagnosed with HeFH after he had a myocardial infarction at 33 years of age. By DNA sequence analysis, he was found to have a heterozygous splicing mutation in his LDLR gene. This discovery expanded the growing mutational spectrum in patients with HeFH in Ontario. Given that HeFH is a treatable cause of early vascular disease, it is important that this condition be recognized, diagnosed and treated in affected patients; but as yet, there is no consensus on the best approach. Diagnostic criteria based on family history and clinical presentation have been proposed for patients with suspected HeFH. Biochemical or molecular screening might be considered to detect new cases of HeFH in populations with a relatively high HeFH prevalence and a relatively small number of possible causative mutations. So far, however, the most cost-effective and efficient systematic strategy to detect previously undiagnosed cases of HeFH is still cascade testing: clinical and biochemical screening of close relatives of the proband patient diagnosed with HeFH. Pharmacologic treatment of HeFH is cost-effective.

Ray JG, Diamond P, Singh G, Bell CM. · Department of Medicine, St Michael's Hospital, University of Toronto, Toronto, Ontario, Canada. · BJOG. · Pubmed #16553649 No free full text.

Abstract: BACKGROUND: Features of the metabolic syndrome-maternal obesity, diabetes mellitus and chronic hypertension-are risk factors for pre-eclampsia. OBJECTIVES: To determine the risk of pre-eclampsia in the presence of maternal hypertriglyceridemia, another major element of the metabolic syndrome. SEARCH STRATEGY: Two investigators independently searched PubMed and Embase databases from 1980 to December 2004 for relevant studies. The terms preeclampsia, eclampsia, pregnancy-induced hypertension or toxemia were combined with dyslipidemia, hyperlipidemia, hypertriglyceridemia, lipids, cholesterol, triglycerides (TG) or lipoprotein. SELECTION CRITERIA: We included case-control and cohort studies published in English that included at least 20 women with pre-eclampsia and that sampled serum or plasma TG at any time before, during or after pregnancy. DATA COLLECTION AND ANALYSIS: Mean maternal TG concentrations were compared between cases and controls within each study. The odds ratio of pre-eclampsia was calculated by comparing the risk of pre-eclampsia among women in each higher TG concentration category with that in the lowest reference category. MAIN RESULTS: A total of 19 case-control and 3 prospective cohort studies were included. In 14 studies, the mean TG concentration was significantly higher among pre-eclamptic cases than among unaffected controls; in seven other studies, there was a nonsignificant trend in the same direction. The risk of pre-eclampsia typically doubled with each increasing TG category. In the four studies that adjusted for potential confounders, such as maternal age, parity and body mass index, there was about a four-fold higher risk of pre-eclampsia in the highest relative to the lowest TG category. AUTHOR'S CONCLUSIONS: There exists a consistent positive association between elevated maternal TG and the risk of pre-eclampsia. Given that maternal hypertriglyceridemia is a common feature of the metabolic syndrome, interventional studies are needed to determine whether pre-pregnancy weight reduction and dietary modification can lower the risk of pre-eclampsia.

Manuel DG, Lim J, Tanuseputro P, Anderson GM, Alter DA, Laupacis A, Mustard CA. · Institute for Clinical Evaluative Sciences, G106-2075 Bayview Avenue, Toronto, ON, Canada M4N 3M5. · BMJ. · Pubmed #16543339 links to  free full text

This publication has no abstract.

Marinangeli CP, Varady KA, Jones PJ. · School of Dietetics and Human Nutrition, McGill University, Québec, Canada. · J Nutr Biochem. · Pubmed #16410048 No free full text.

Abstract: At present, dyslipidemia is most commonly treated with lipid-altering pharmacological therapies. However, safety concerns regarding the use of these agents have prompted the need for safe and efficacious nonpharmacological lipid-altering interventions. One such natural therapy is the combination of plant sterols and endurance training. This combination lifestyle intervention has been shown to decrease total cholesterol, low-density lipoprotein (LDL) cholesterol and triglyceride concentrations while increasing high-density lipoprotein (HDL) cholesterol concentrations. However, the mechanisms that underlie these positive lipid alterations have yet to be clarified. Thus, the purpose of this review is to evaluate individual effects of plant sterols and exercise training on lipid levels while attempting to elucidate the possible independent and synergistic mechanisms of action responsible for these modulations. Results reveal that plant sterols decrease both total and LDL cholesterol levels by reducing exogenous cholesterol absorption by way of cholesterol displacement in the intestinal lumen. Additionally, the intestinal membrane transport proteins, ABCG5, ABCG8, as well as NPC1L1, have also been implicated in plant sterol-mediated cholesterol lowering. Conversely, exercise decreases triglyceride levels by reducing hepatic very low-density lipoprotein secretion and increasing skeletal lipoprotein lipase activity. In addition, endurance training was shown to increase HDL cholesterol levels by way of HDL subfraction alterations, in conjunction with changing reverse cholesterol transport enzyme activities. Moreover, plant sterols and exercise may work synergistically to alter lipid levels by modulating lipoprotein transport, composition, release and metabolism. In sum, the present review lends further insight as to the metabolic benefits of adopting a healthy lifestyle, including plant sterols and endurance training, in the treatment of dyslipidemia.

Poulin MJ, Cortese L, Williams R, Wine N, McIntyre RS. · Centre Hospitalier Affilié Universitaire de Québec, Hôpital de l'Enfant-Jésus, Quebec. · Can J Psychiatry. · Pubmed #16262112 No free full text.

Abstract: OBJECTIVES: To provide practical recommendations for monitoring patients both before and during treatment with atypical antipsychotics, to assist clinicians in implementing preventative measures against diabetes, and to establish baselines according to which clinicians should initiate diabetes treatment. METHOD: A working group of Canadian specialists in psychiatry and endocrinology reviewed peer-reviewed clinical studies published in this area and other relevant papers and abstracts. RESULTS: The reviewed studies further confirm that atypical antipsychotic medications are the most effective components in the medical management of many psychotic conditions; they also further emphasize the need to more stringently monitor and recognize diabetes risk factors inherent in these patients. Recommendations are based on a review of the available data, on expert opinion and consensus, and on current Canadian guidelines for the treatment of schizophrenia and management of diabetes. CONCLUSIONS: Patients with psychiatric disorders, most particularly schizophrenia and mood disorders, have an increased risk for type 2 diabetes and should be screened frequently, especially when other risk factors are present. The resulting recommendations offer practical steps for effectively screening patients prior to and during treatment with atypical antipsychotics. They include (1) how to conduct an initial baseline assessment, (2) when and how to monitor blood glucose and lipid levels, and (3) how to educate patients regarding such lifestyle issues as nutrition, exercise, and diet.

Perrault LP, Carrier M. · Research Centre, Department of Surgery, Montreal Heart Institute, Quebec, Canada. · Can J Cardiol. · Pubmed #16234893 links to  free full text

Abstract: BACKGROUND: Despite the successes and advances made in clinical heart transplantation, the number one culprit and greatest cause of death beyond the first year remains graft coronary vasculopathy. The study of the central role of the endothelium in the development of graft coronary vasculopathy has been aided by the numerous advances in basic science, which have enhanced our understanding of endothelial physiology. METHODS: Several experimental strategies are reviewed, such as the in vivo porcine heterotopic heart transplantation model and the in vivo and in vitro exposure of coronary and renal arteries to immunosuppressive drugs. Other studies are reviewed, including vascular biology studies that examine the role of acute and chronic rejection, hypercholesterolemia, inhibition of endothelial nitric oxide synthase, denudation of the endothelium, and immunosuppressive drugs in coronary endothelial function and intimal hyperplasia; studies that assess the acute and remote effects of different cardioplegic and preservation solutions used for transplantation; and studies that test novel therapies for pulmonary endothelial dysfunction and hypertension. RESULTS: These studies highlight the target factors that ensure preservation of the protective role of the coronary endothelium on the vascular wall, including the control of immunological damage, treatment of hypercholesterolemia, use of optimal cardioplegic and preservation strategies, and the prevention and treatment of pulmonary endothelial dysfunction after exposure to cardiopulmonary bypass and heart transplantation. CONCLUSION: Further research should focus on improving human lymphocyte antigen matching of donor and recipients, improving immunosuppressive regimens, and preserving graft coronary endothelial function and the pulmonary circulation to positively modify the survival curve of transplant recipients.

Koschinsky ML. · Department of Biochemistry, Queen's University, A208 Botterell Hall, Kingston, ON K7L 3N6, Canada. · Curr Atheroscler Rep. · Pubmed #16105483 No free full text.

Abstract: Although elevated plasma concentrations of lipoprotein(a) (Lp(a)) have been identified as a risk factor for coronary heart disease, the pathophysiologic and physiologic roles of Lp(a) continue to elude basic researchers and clinicians alike. Lp(a) is a challenging lipoprotein to study because it has a complex structure consisting of a low-density lipoprotein-like moiety to which is covalently attached the unique glycoprotein apolipoprotein(a) (apo(a)). Apo(a) contains multiply repeated kringle domains that are similar to a sequence found in the fibrinolytic proenzyme plasminogen; differing numbers of kringle sequences in apo(a) give rise to Lp(a) isoform size heterogeneity. In addition to elevated plasma concentrations of Lp(a), apo(a) isoform size has been identified as a risk factor for coronary heart disease, although studies addressing this relationship have been limited. The similarity of Lp(a) to low-density lipoprotein and plasminogen provides an enticing link between the processes of atherosclerosis and thrombosis, although a clear demonstration of this association in vivo has not been provided. Clearly, Lp(a) is a risk factor for both atherothrombotic and purely thrombotic events; a plethora of mechanisms to explain these clinical findings has been provided by both in vitro studies as well as animal models for Lp(a).

Kundhal K, Pierratos A, Chan CT. · Division of Nephrology, Department of Medicine, Toronto General Hospital-University Health Network, 12 Eaton North, 200 Elizabeth Street, Toronto, Ontario M5G 2C4, Canada. · Cardiol Clin. · Pubmed #16084286 No free full text.

Abstract: Cardiovascular disease remains the leading cause of morbidity and mortality for patients with end-stage renal disease. Conventional hemodialysis has had limited impact on cardiovascular risk factors and mortality. Increasing evidence suggests that nocturnal home hemodialysis has beneficial effects on cardiovascular parameter outcomes. This article reviews the documented effects of nocturnal home hemodialysis on blood pressure control, cardiac geometry and left ventricular systolic function, lipid profiles, calcium-phosphate metabolism, parathyroid hormone levels, homocysteine levels, sleep apnea, and autonomic modulation of heart rate. It discusses possible mechanisms to explain these observed changes.