Hyperlipidemias: Sweden

Rydén L, Standl E, Bartnik M, Van den Berghe G, Betteridge J, de Boer MJ, Cosentino F, Jönsson B, Laakso M, Malmberg K, Priori S, Ostergren J, Tuomilehto J, Thrainsdottir I, Vanhorebeek I, Stramba-Badiale M, Lindgren P, Qiao Q, Priori SG, Blanc JJ, Budaj A, Camm J, Dean V, Deckers J, Dickstein K, Lekakis J, McGregor K, Metra M, Morais J, Osterspey A, Tamargo J, Zamorano JL, Deckers JW, Bertrand M, Charbonnel B, Erdmann E, Ferrannini E, Flyvbjerg A, Gohlke H, Juanatey JR, Graham I, Monteiro PF, Parhofer K, Pyörälä K, Raz I, Schernthaner G, Volpe M, Wood D, Anonymous00256, Anonymous00257. · Department of Cardiology, Karolinska University Hospital, Sweden. · Eur Heart J. · Pubmed #17220161 links to  free full text

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Olsson AG, Nilsson PM. · Institutionen för medicin och hälsa, Hälsouniversitetet, Linköping. · Lakartidningen. · Pubmed #19452786 No free full text.

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Jönsson-Rylander AC, Lundin S, Rosengren B, Pettersson C, Hurt-Camejo E. · AstraZeneca, R&D, Bioscience, Mölndal S-431 83, Wallenberg Laboratory for Cardiovascular Research, Sahlgrenska University Hospital, Gotheburg, Sweden. · Curr Atheroscler Rep. · Pubmed #18489854 No free full text.

Abstract: Elevated circulating levels of secretory phospholipase A(2) (sPLA(2)) are associated with atherosclerotic cardiovascular disease. sPLA(2) can contribute to atherogenesis by hydrolyzing phospholipids of circulating lipoproteins and lipoproteins entrapped in the arterial wall and/or in cells that reside in the intima and that participate in the inflammatory response to lipoprotein deposition. This article reviews differences and similarities between sPLA(2)-IIA, sPLA(2)-V, and sPLA(2)-X, all of which are members of this family of enzymes with reported potential proatherogenic features. Published data suggest that each of the enzymes has a distinct profile characterized by differences in tissue expression and localization, capacity to act on phospholipids of cell membranes and lipoproteins, and their interaction with arterial proteoglycans. In addition, the article discusses results from the authors' laboratory showing that diet-induced or gene-induced hyperlipidemia in mice enhances the expression of sPLA(2)-V in different tissues, but not sPLA(2)-IIA. Such differences indicate that these enzymes may have different roles in atherosclerotic cardiovascular disease through their distinct profiles.

Kivipelto M, Solomon A. · Aging Research Center, Karolinska Institutet, Gavlegatan 16, S-113 30 Stockholm, Sweden. · J Nutr Health Aging. · Pubmed #18165854 No free full text.

Abstract: Several vascular and lifestyle related factors have been suggested to influence the development of dementia and Alzheimer's disease (AD), creating new prevention opportunities. This paper discusses current epidemiological evidence and new findings from the Finnish population based CAIDE study linking some of these factors to dementia/AD. Such findings provide an optimistic outlook especially for persons with genetic susceptibility; it may be possible to reduce the risk or postpone the onset of dementia by adopting healthy lifestyle options. The interplay of genes and environment in the aetiology of AD needs to be further investigated as well as the role of lifestyle and pharmacological interventions for the prevention of dementia.

Qiu C, De Ronchi D, Fratiglioni L. · Aging Research Center, Department of Neurobiology, Caring Sciences and Society (NVS), Karolinska Institutet and the Stockholm Gerontology Research Center, Stockholm, Sweden. · Curr Opin Psychiatry. · Pubmed #17551353 No free full text.

Abstract: PURPOSE OF REVIEW: The epidemiology of dementia is one of the priority fields in aging research. This review aims to highlight the most relevant findings over last years concerning occurrence, risk factors, and prevention of dementia and its major subtypes. RECENT FINDINGS: It is estimated that currently around 24 million people have dementia in the world, with the number being projected to double every 20 years, and that 60% of dementia patients live in developing countries, with the proportion being raised to more than 70% by 2040. Current evidence suggests that vascular factors, such as midlife hypertension, diabetes, and cerebrovascular disease, contribute significantly to the development of dementia and Alzheimer's disease, and that active engagement in mental, physical, and social activities may postpone the onset of dementia by providing cognitive reserve. SUMMARY: Dementia represents a major public health challenge as a consequence of rapid increase in the aging population worldwide, especially in developing countries. This challenge can be partly confronted by successful development of preventive strategies. Evidence has emerged that proper control of vascular disorders and maintenance of active lifestyles may prevent or delay the onset and progression of dementia and Alzheimer's disease. Intervention trials are warranted to determine, to what extent, such programs are effective against dementia.

Höglund K, Blennow K. · Department of Neuroscience and Physiology, Section of Psychiatry and Neurochemistry at the Sahlgrenska Academy, Göteborg University, Göteborg, Sweden. · CNS Drugs. · Pubmed #17521225 No free full text.

Abstract: To date, a number of hypotheses of the cause of Alzheimer's disease, the most common form of dementia, have been postulated. The beta-amyloid peptide (Abeta) is the major constituent of senile plaques, which together with atrophy and neurofibrillary tangles, is the main neuropathological finding in Alzheimer's disease. It is a widely accepted theory that aggregation of Abeta into plaques is an initial event in the pathogenesis of Alzheimer's disease, driving neurodegeneration. The cholesterol hypothesis, primarily based on in vitro and animal studies, states that increased levels of cholesterol promote the production of Abeta. Furthermore, treating animals with HMG-CoA reductase inhibitors ('statins'; cholesterol-lowering agents), or adding these agents to cell culture, results in decreased production of Abeta. This 'positive' effect of statin treatment has further been verified by some, but not all, longitudinal studies where a reduced prevalence of Alzheimer's disease is seen among patients taking statins. These findings have together been interpreted to indicate that statins act via a cholesterol-dependent mechanism, reducing the production of Abeta and, hence, the risk of developing Alzheimer's disease.This review focuses on the cholesterol hypothesis of Alzheimer's disease and investigations into its validity in the clinical setting, i.e. the outcome of clinical trials where the effect of statin treatment on Abeta production has been studied. To date, the cholesterol hypothesis has not been shown to be valid in clinical trials. We hypothesise that the vascular contributions in Alzheimer's disease may be one possible mechanism for statins to interfere with the disease process and reduce the prevalence of Alzheimer's disease. We also suggest that statins may act through the inflammatory pathway. Both of these mechanistic suggestions are good candidates, supported by the literature, for the underlying mechanistic link between statin treatment and a reduced prevalence for Alzheimer's disease.

Gottsäter A, Wahlberg E. · Kliniken för kärlsjukdomar, Universitetssjukhuset MAS, Malmö. · Lakartidningen. · Pubmed #17447582 No free full text.

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Ellegård LH, Andersson SW, Normén AL, Andersson HA. · Department of Clinical Nutrition, Sahlgrenska Academy at Göteborg University, Box 459, SE-413 90 Göteborg, Sweden · Nutr Rev. · Pubmed #17310858 No free full text.

Abstract: Plant sterols, naturally occurring in foods of plant origin, reduce cholesterol absorption. Experimental studies show plant sterols to be an important part of the serum-cholesterol lowering effect of certain diets and dietary components. Epidemiological data show that individuals with higher intakes of plant sterols from their habitual diets have lower serum-cholesterol levels. To date, the role of naturally occurring plant sterols for lowering serum cholesterol has probably been underestimated. The consumption of dietary plant sterols should be a part of dietary advice to patients with hypercholesterolemia and the general public for the prevention and management of coronary heart disease.

Rudling M. · Kliniken för endokrinologi, metabolism och diabetes, institutionen för medicin, Karolinska Universitetssjukhuset Huddinge, samt Centrum för nutrition och toxikologi, Novum, Stockholm · Lakartidningen. · Pubmed #17117659 No free full text.

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Rosengren B, Jönsson-Rylander AC, Peilot H, Camejo G, Hurt-Camejo E. · AstraZeneca, R&D, Molecular Pharmacology, Mölndal S-431 83, Sweden. · Biochim Biophys Acta. · Pubmed #17070102 No free full text.

Abstract: Clinical observations strongly support an association of circulating levels of secretory phospholipases A(2) (sPLA(2)) in atherosclerotic cardiovascular disease (ACVD). Two modes of action can provide causal support for these statistical correlations. One is the action of the enzymes on circulating lipoproteins and the other is direct action on the lipoproteins once in the arterial extracellular intima. In this review we discuss results suggesting a distinct profile of characteristics related to localization, action on plasma lipoproteins and interaction with arterial proteoglycans for sPLA(2)-IIA and sPLA(2)-V. The differences observed indicate that these enzymes may contribute to atherosclerosis through dissimilar pathways. Furthermore, we comment on recent animal studies from our laboratory indicating that the expression of type V enzyme is up-regulated by genetically and nutritionally-induced dyslipidemias but not the group type IIA enzyme, which is well known to be up-regulated by acute inflammation. The results suggest that if similar up-regulation occurs in humans in response to hyperlipidemia, it may create a distinctive link between the group V enzyme and the disease.

Björkhem I, Heverin M, Leoni V, Meaney S, Diczfalusy U. · Division of Clinical Chemistry, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden. ingemar.bjö · Acta Neurol Scand Suppl. · Pubmed #16866910 No free full text.

Abstract: There is a clear link between cholesterol turnover and neurodegenerative diseases and hypercholesterolemia is an established risk factor for Alzheimer's disease (AD). The failure to demonstrate a transfer of cholesterol from the circulation into the brain in humans and experimental animals makes it difficult to explain the link between hypercholesterolemia and AD. In contrast to cholesterol itself, side-chain oxidized cholesterol metabolites such as 24S-hydroxycholesterol and 27-hydroxycholesterol are able to pass the blood-brain barrier (BBB). Formation of 24S-hydroxycholesterol is the quantitatively most important mechanism for elimination of cholesterol from the brain and we recently demonstrated a significant net uptake of 27-hydroxycholesterol by the brain from the circulation. We have also shown that patients with AD have increased brain levels of 27-hydroxycholesterol, which may affect the production of beta-amyloid in the brain. The levels of 27-hydroxycholesterol in the circulation are correlated with the levels of cholesterol and the possibility must be considered that the flux of 27-hydroxycholesterol into the brain is the missing link between hypercholesterolemia and Alzheimer's disease. Current knowledge about the role of the two oxysterols for cholesterol homeostasis in the brain as well as their diagnostic potential are reviewed.

Ravnskov U, Rosch PJ, Sutter MC, Houston MC. · Magle Stora Kyrkogata 9, S 22350 Lund, Sweden. · BMJ. · Pubmed #16740566 links to  free full text

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Gottsäter A. · University of Lund, Department of Vascular Diseases, Malmö University Hospital, S-205 02 Malmö, Sweden. · Eur J Vasc Endovasc Surg. · Pubmed #16631394 No free full text.

Abstract: OBJECTIVE: To review the best medical management of critical limb ischaemia (CLI). METHODS: Published studies dealing with CLI and risk factors were searched for via PUBMED. FINDINGS AND CONCLUSIONS: Patients with critical limb ischaemia (CLI) have a one and ten year mortality of approximately 20% and 75% respectively. Risk factors for the development of peripheral atherosclerosis are the same as for coronary and cerebrovascular atherosclerosis namely diabetes mellitus, hyperlipidaemia, arterial hypertension, and smoking. As there are few studies of risk factor for peripheral arterial occlusive disease (PAOD), treatment recommendations are often based on studies in patients with coronary or cerebrovascular atherosclerosis. While waiting for specific studies, CLI patients should be treated according to current guidelines for other atherosclerotic patients.

Wahlberg G. · Kvartersakuten Serafen och Karolinska institutet, Danderyds sjukhus, Stockholm. · Lakartidningen. · Pubmed #16465756 No free full text.

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Erhardt LR, Gotto A. · Department of Cardiology, Cardiology Research Unit, University of Lund, Malmö University Hospital, SE-205 02 Malmö, Sweden. · Atherosclerosis. · Pubmed #16309687 No free full text.

Abstract: Cardiovascular disease (CVD) is the leading cause of death in Europe and the US. This paper reviews the evolution of the Joint European Societies' guidelines with respect to their lipid recommendations. We stress the importance of lowering lipid levels to, or below, the currently recommended goals and argue that patients' global risk for CVD, rather than baseline lipid levels, should direct the intensity of lipid-lowering treatment. However, the emphasis on near-term (i.e., in the next 10 years) global risk estimation may under-emphasize the importance of considering lifetime cardiovascular risk in treatment decisions. Although various guidelines' thresholds for treatment initiation and recommended goals differ, they are similar in the theme of treating global risk. Most clinical trials have not identified a threshold of cholesterol level beyond which lowering cholesterol levels no longer provides cardiovascular benefit. An urgent call for action is needed to improve goal attainment in patients with or at risk for CVD. Improving access to risk-reducing treatments should be a priority.

Olofsson SO, Borèn J. · Wallenberg Laboratory for Cardiovascular Research, Göteborg University, Sahlgrenska University Hospital, Göteborg, Sweden. · J Intern Med. · Pubmed #16238675 No free full text.

Abstract: Apolipoprotein (apo) B exists in two forms apoB100 and apoB48. ApoB100 is present on very low-density lipoproteins (VLDL), intermediate density lipoproteins (IDL) and LDL. ApoB100 assembles VLDL particles in the liver. This process starts by the formation of a pre-VLDL, which is retained in the cell unless converted to the triglyceride-poor VLDL2. VLDL2 is secreted or converted to VLDL1 by a bulk lipidation in the Golgi apparatus. ApoB100 has a central role in the development of atherosclerosis. Two proteoglycan-binding sequences in apoB100 have been identified, which are important for retaining the lipoprotein in the intima of the artery. Retention is essential for the development of the atherosclerotic lesion.

Sjögren M, Blennow K. · Section of Experimental Geriatrics, Neurotec, Karolinska Institute KFC, Novum Plan 4, SE-14186 Huddinge, Sweden. · World J Biol Psychiatry. · Pubmed #16156481 No free full text.

Abstract: A leading hypothesis on the pathophysiology of Alzheimer's disease (AD) is the mis-metabolism of amyloid precursor protein. This mis-metabolism causes the 42-amino acid form of A beta(Abeta42) to form oligomers that in turn start a chain of events leading to the accumulation of amyloid plaques. Vascular factors such as hypertension, hypercholesterolemia and diabetes as well as the inheritance of the epsilon4 allele of the ApoE gene are risk factors for AD. These risks are thought to promote the production of beta-amyloid (Abeta). An association between cholesterol and the development of AD was suggested in 1994 and since then, research has confirmed a link between cholesterol and the development of AD. A high cholesterol level in mid-life is a risk for AD and statins i.e. cholesterol-lowering drugs, reduce this risk. Statins inhibit enzymes involved in the endogenous synthesis of cholesterol and evidence is mounting that they also affect enzymes in Abeta metabolism i.e. beta-secretase. This normalises the breakdown of the precursor of Abeta, amyloid precursor protein, thereby promoting the nonamyloidogenic pathway. This review focusses on the link between cholesterol and Alzheimer's disease.

Carlson LA. · King Gustaf V Research Institute, Karolinska Institutet, Stockholm, Sweden. · J Intern Med. · Pubmed #16018787 No free full text.

Abstract: Nicotinic acid has, like the Roman God Janus, two faces. One is the vitamin. The other is the broad-spectrum lipid drug. The Canadian pathologist Rudolf Altschul discovered 50 years ago that nicotinic acid in gram doses lowered plasma levels of cholesterol. From the point of view of treatment of the dyslipidaemias that are risk factors for clinical atherosclerosis nicotinic acid is a miracle drug. It lowers the levels of all atherogenic lipoproteins--VLDL and LDL with subclasses as well as Lp(a)--and in addition it raises more than any other drug the levels of the protective HDL lipoproteins. Trials have shown that treatment with nicotinic acid reduces progression of atherosclerosis, and clinical events and mortality from coronary heart disease. The new combination treatment with statin-lowering LDL and nicotinic acid-raising HDL is reviewed. A basic effect of nicotinic acid is the inhibition of fat-mobilizing lipolysis in adipose tissue leading to a lowering of plasma free fatty acids, which has many metabolic implications which are reviewed. The very recent discovery of a nicotinic acid receptor and the finding that the drug stimulates the expression of the ABCA 1 membrane cholesterol transporter have paved the way for exciting and promising new 50 years in the history of nicotinic acid.

Frostegård J. · Department of Medicine, Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden. · J Intern Med. · Pubmed #15910552 No free full text.

Abstract: Atherosclerosis is an inflammatory disease and the major cause of cardiovascular disease (CVD) in general. Atherosclerotic plaques are characterized by the presence of activated immune competent cells, but antigens and underlying mechanisms causing this immune activation are not well defined. During recent years and with improved treatment of acute disease manifestations, it has become clear that the risk of CVD is very high in a prototypic autoimmune disease, systemic lupus erythematosus (SLE). SLE-related CVD and atherosclerosis are important clinical problems but may in addition also shed light on how immune reactions are related to premature atherosclerosis and atherothrombosis. A combination of traditional and nontraditional risk factors, including dyslipidaemia (and to a varying degree hypertension, diabetes and smoking), inflammation, antiphospholipid antibodies (aPL) and lipid oxidation are related to CVD in SLE. Premature atherosclerosis in some form leading to atherothrombosis is likely to be a major underlying mechanism, though distinctive features if any, of SLE-related atherosclerosis when compared with 'normal' atherosclerosis are not clear. One interesting possibility is that factors such as inflammation or aPL make atherosclerotic lesions in autoimmune disease more prone to rupture than in 'normal' atherosclerosis. Whether premature atherosclerosis is a general feature of SLE or only affects a subgroup of patients remains to be demonstrated. Treatment of SLE patients should also include a close monitoring of traditional risk factors for CVD. In addition, attention should also be paid to nontraditional risk factors such as inflammation and SLE-related factors such as aPL. Hopefully novel therapeutic principles will be developed that target the causes of the inflammation and immune reactions present in atherosclerotic lesions.

Hansson GK. · Karolinska Institute, Center for Molecular Medicine, Department of Medicine, Karolinska University Hospital, Stockholm, Sweden. · N Engl J Med. · Pubmed #15843671 No free full text.

This publication has no abstract.

Berkenstam A, Färnegårdh M, Gustafsson JA. · Karo Bio AB, Novum 141 57 Huddinge, Sweden. · Mech Ageing Dev. · Pubmed #15541766 No free full text.

Abstract: Members of the nuclear receptor gene family act as biological rheostats to maintain metabolic homeostasis in response to endocrine and nutritional changes. The liver X (LXR) and thyroid hormone (TR) receptors have been shown to regulate overlapping but distinct metabolic pathways important for overall lipid homeostasis. Dyslipidemia is one out of four key determinants for cardiovascular risk and both LXRs and TRs may provide attractive targets for intervention of cardiovascular disease. In this review we will compare the two receptor systems to highlight similarities and differences in structure and function with implications for development of novel treatments for dyslipidemia and atherosclerosis.

Carlson LA. · King Gustaf V Research Institute, Karolinska Hospital, Stockholm, Sweden. · Int J Clin Pract. · Pubmed #15311728 No free full text.

Abstract: Niacin (nicotinic acid) is the broad-spectrum lipid drug, which lowers the concentration of all atherogenic plasma lipids/lipoproteins and at the same time raises the levels of the protective HDL (high-density lipoprotein). Niaspan is a prolonged release (PR) formulation of niacin, which has considerable advantages over both immediate release (IR) and slow release (SR) formulations of this drug. The major early side effect of IR niacin, the flush, is reduced with Niaspan. The hepatotoxic effects with SR niacin are not present with Niaspan. It is suitable for once daily prescription at bedtime. Niaspan is effective as monotherapy and in combination with other lipid-lowering drugs such as statins and fibrates. It is particularly useful for treatment of the dyslipidaemia of type 2 diabetes, where IR but not PR niacin may deteriorate the diabetic condition. Overall, niacin, now available as the well-tolerable drug formulation Niaspan, is the unique broad-spectrum lipid drug for the prevention and treatment of clinical atherosclerosis.

Stegmayr B, Lalau JD, Johnson O. · Department of Internal Medicine, University Hospital, SE90185 Umeå, Sweden. · Transfus Apher Sci. · Pubmed #15172626 No free full text.

Abstract: Based on a large body of evidence, high LDL-cholesterol concentrations in blood is a key factor of coronary heart disease (CHD). Overall, the observational studies show a curvilinear relationship between blood cholesterol level and coronary heart disease risk. Even more relevant are the randomised trials, firmly establishing that within just a few years a cholesterol-lowering therapy confers a dramatic effect on cardiovascular morbidity and mortality. More recent studies indicate that there is a greater risk reduction in those subjects achieving lower low-density lipoprotein cholesterol (LDL-C) levels--i.e. lower is better. While this favours aggressive therapy, it is nevertheless imperative to precise patients selection for every therapy that entails a major commitment for the patient and medical community. Therefore, well-defined criteria for use of LDL-apheresis have yet to be established in the light of the expanding therapeutic armamentarium. Based on the current knowledge of the impact of statin therapy and anticipating that new options will further optimize the management of dyslipidemia in high-risk patients, we propose a reliable assessment of the effects of LDL-apheresis.

Melkersson K, Dahl ML. · Psychiatric Polyclinic, Sollentuna Hospital, Nytorpsvägen 10-12, SE-191 35 Sollentuna, Sweden. · Drugs. · Pubmed #15025545 No free full text.

Abstract: Adverse metabolic effects, such as diabetes mellitus, lipid abnormalities and weight gain, have increasingly been recognised with the use of the newer, so-called atypical antipsychotic drugs. This article reviews the current literature in the field and attempts to answer the question of whether the atypical antipsychotics differ in their effects on glucose-insulin homeostasis and lipid metabolism. It also addresses how then to manage the use of the atypical antipsychotics that do interfere with these metabolic systems. Differences in effects of atypical antipsychotics on leptin levels are also summarised and put into context; bodyweight gain associated with atypical antipsychotics is reviewed elsewhere.In summary, there are no large controlled trials published quantifying the prevalence of adverse effects on glucose-insulin homeostasis and lipid metabolism in patients receiving atypical antipsychotics. Nevertheless, the published articles and case reports reviewed in this article give a fairly good view of those adverse effects occurring with clozapine, olanzapine and risperidone, whereas little data are available regarding quetiapine, ziprasidone and zotepine, and no data exist for amisulpride and aripiprazole. Estimated rankings of the atypical agents, based on the available literature, show that the relative risk of glucose intolerance/diabetes mellitus, hyperlipidaemia and hyperleptinaemia is highest for clozapine and olanzapine, moderately high for quetiapine, rather low for risperidone and lowest for ziprasidone. Since adverse metabolic effects of atypical antipsychotics may have a negative influence on both the antipsychotic treatment outcome as well as the physical health of the patient, these effects have to be recognised and adequately managed. In this review, recommendations for prevention and treatment of the adverse metabolic effects are outlined.

Olsson A. · Linköping University, Sweden. · Int J Clin Pract Suppl. · Pubmed #14649698 No free full text.

This publication has no abstract.