Hyperlipidemias: Sweden

Skoog I, Gustafson D. · Institute of Clinical Neuroscience, Section of Psychiatry, Sahlgrenska Hospital, Göteborg University, Göteborg, Sweden. · Neurol Res. · Pubmed #14503023 No free full text.

Abstract: Hypertension is a risk factor for stroke, ischemic white matter lesions, silent infarcts, general atherosclerosis, myocardial infarction and cardiovascular morbidity and mortality. This risk increases with increasing blood pressure also at blood pressure within the normal ranges, and a high percentage of these cardiovascular events occur in those with normal blood or mild hypertension. Several studies have reported that high blood pressure precedes Alzheimer's disease by decades, but blood pressure decreases the years before dementia onset and is lower in individuals with Alzheimer's disease than in controls. High blood pressure has also been related to the neuropathological manifestations of Alzheimer's disease. Hypertension often clusters with other vascular risk factors, including diabetes mellitus, obesity, and hypercholesterolemia. Also, these risk factors have been related to Alzheimer's disease. The exact mechanism behind these associations is not clear. Hypertension may cause cerebrovascular disease that may increase the likelihood that individuals with AD encephalopathy will express a dementia syndrome, but hypertension may also accelerate the AD process, subclinical AD may lead to increased blood pressure, and similar biological mechanisms may be involved in the pathogenesis of both disorders. Hypertension is a common disorder and often untreated. Even if hypertension only results in a moderately increased risk of AD, or overall dementia, better treatment of hypertension may have an immense effect on the total numbr of demented individuals.

Blomberg P, Smith CI. · Clinical Research Center, Karolinska Institutet, Huddinge University Hospital, SE-141 86 Stockholm, Sweden. · Expert Opin Biol Ther. · Pubmed #12943453 No free full text.

Abstract: The concept of gene therapy involves the introduction of genetic material into patient cells to cure or alleviate the symptoms of a disease by complementing a damaged gene or by giving the cell a new function. The belief that gene therapy would soon reach the clinic has been widely spread, frequently resulting in controversies when these expectations were not met. Nevertheless, over the last 10-year period, the experience from a number of clinical trials has taught us that gene transfer is technically feasible, but that the gene delivery vehicles, or vectors, for the transfer of genetic material are still suboptimal and that treatment may have severe side effects. This review will provide examples of different genetic disorders for which gene therapy is an option and has been attempted. It will also briefly discuss the existing vector systems and mention their advantages and drawbacks.

Camejo G. · AstraZeneca, Mölndal, Sweden. · Int J Clin Pract Suppl. · Pubmed #12793596 No free full text.

Abstract: Augmented release of non-esterified fatty acids (NEFA) from insulin-resistant adipocytes appears to be the main cause of the 'atherogenic lipoprotein profile' associated with insulin resistance and type 2 diabetes. This atherogenic profile is characterised by large very-low-density lipoproteins (VLDL), small, dense low-density lipoproteins (LDL) and low levels of high-density lipoproteins (HDL), resulting in deposition of apo B lipoproteins in the vascular intima and subsequent inhibition of reverse cholesterol transport. This lipoprotein retention also results in a proinflammatory response from the vascular endothelium, which is increased in insulin resistance. Thus the ideal therapy for insulin resistance, and its complications, should both improve its associated dyslipidaemia and ameliorate the vascular atherogenic reaction. Some peroxisome proliferator-activated receptor (PPAR)-gamma and dual PPARalpha/gamma agonists improve insulin resistance and its dyslipidaemia, both in rodents and man, while in animal models they can show clear antiatherosclerotic effects. Nonetheless, it is difficult to evaluate how much of these antiatherosclerotic actions are caused by effects on the dyslipidaemia or by direct effects on vascular cells. Upregulation of PPARgamma and PPARalpha/gamma activity in macrophages can reduce secretion of proinflammatory cytokines and matrix metalloproteases, as well as increase HDL-mediated cholesterol efflux transport--all potentially antiatherosclerotic results. In addition, treatment of smooth muscle cells with PPARgamma agonists can partially revert possible atherogenic changes in the production of matrix proteoglycans induced by exposure to NEFA. Although these findings are still preliminary, and their relevance to human atherosclerosis has not been fully elaborated, these results suggest that improved PPARalpha/gamma agonism may positively modulate several of the metabolic steps connecting insulin resistance with dyslipidaemia and with the atherogenic response.

Fellström BC, Holdaas H, Jardine AG. · Department of Medicine, Western Infirmary, Glasgow, United Kingdom. · Kidney Int Suppl. · Pubmed #12694345 No free full text.

Abstract: BACKGROUND: The risk of cardiovascular complications is markedly increased in patients on dialysis treatment. This includes cardiac disease, stroke, and peripheral vascular disease. The mortality in dialysis patients is markedly higher compared to a nonuremic population. There are several cardiovascular (CV) risk factors that are unique to this population, one of which is dyslipidemia. Uremic patients do not usually develop hypercholesterolemia, but rather are characterized by high levels of very low density lipoprotein (VLDL) triglycerides, low high density lipoprotein (HDL) cholesterol, and elevated levels of modified low density lipoprotein (LDL) particles, which are particularly harmful to the vascular wall. HMG-CoA reductase inhibitors (statins) have been proven to be very efficient in reducing CV events in a nonrenal population. There are several landmark trials that have demonstrated that statins reduce the mortality in cardiovascular disease (CVD) in populations with normal, or close to normal, renal function. There are some observational registry data indicating that this may also be true in hemodialysis (HD) patients, but no prospective controlled trial has been performed to date. METHODS: We present the rationale for, and a brief outline of, a randomized placebo-controlled trial using a novel drug, rosuvastatin, in HD patients, to target cardiovascular events (the AURORA study). This study will include close to 3000 male and female HD patients, aged 50-80 years. The study is event driven and it has been estimated that it will run for a follow-up time close to four years. CONCLUSION: There is a sound rationale for making a randomized placebo-controlled statin trial in HD patients, with the objective to demonstrate an effect on CV mortality and morbidity.

Attman PO, Samuelsson O, Johansson AC, Moberly JB, Alaupovic P. · Department of Nephrology, Sahlgrenska University Hospital, Göteborg, Sweden. · Kidney Int Suppl. · Pubmed #12694322 No free full text.

Abstract: Progressive renal failure is accompanied by dyslipidemia, which is reflected in an abnormal apolipoprotein profile. It is characterized by increased concentrations of intact and partially metabolized triglyceride-rich apoB-containing lipoproteins. They occur preferentially in very-low density lipoprotein (VLDL) and low-density lipoprotein (LDL) as a result of impaired metabolism and clearance. Hemodialysis can moderately attenuate the renal dyslipidemia. In contrast, peritoneal dialysis is associated with further aggravation, including an increase of cholesterol-rich apoB-containing lipoproteins.

Olsson AG, McTaggart F, Raza A. · University Hospital, Linköping, Sweden. · Cardiovasc Drug Rev. · Pubmed #12481202 No free full text.

Abstract: Rosuvastatin, a new statin, has been shown to possess a number of advantageous pharmacological properties, including enhanced HMG-CoA reductase binding characteristics, relative hydrophilicity, and selective uptake into/activity in hepatic cells. Cytochrome p450 (CYP) metabolism of rosuvastatin appears to be minimal and is principally mediated by the 2C9 enzyme, with little involvement of 3A4; this finding is consistent with the absence of clinically significant pharmacokinetic drug-drug interactions between rosuvastatin and other drugs known to inhibit CYP enzymes. Dose-ranging studies in hypercholesterolemic patients demonstrated dose-dependent effects in reducing low-density lipoprotein cholesterol (LDL-C) (up to 63%), total cholesterol, and apolipoprotein (apo) B across a 1- to 40-mg dose range and a significant 8.4% additional reduction in LDL-C, compared with atorvastatin, across the dose ranges of the two agents. Rosuvastatin has also been shown to be highly effective in reducing LDL-C, increasing high-density lipoprotein cholesterol (HDL-C), and producing favorable modifications of other elements of the atherogenic lipid profile in a wide range of dyslipidemic patients. In patients with mild to moderate hypercholesterolemia, rosuvastatin has been shown to produce large decreases in LDL-C at starting doses, thus reducing the need for subsequent dose titration, and to allow greater percentages of patients to attain lipid goals, compared with available statins. The substantial LDL-C reductions and improvements in other lipid measures with rosuvastatin treatment should facilitate achievement of lipid goals and reduce the requirement for combination therapy in patients with severe hypercholesterolemia. In addition, rosuvastatin's effects in reducing triglycerides, triglyceride-containing lipoproteins, non-HDL-C, and LDL-C and increasing HDL-C in patients with mixed dyslipidemia or elevated triglycerides should be of considerable value in enabling achievement of LDL-C and non-HDL-C goals in the numerous patients with combined dyslipidemias or metabolic syndrome who require lipid-lowering therapy. Rosuvastatin is well tolerated alone, and in combination with fenofibrate, extended-release niacin, and cholestyramine, and has a safety profile similar to that of currently marketed statins. A large, long-term clinical trials program is under way to investigate the effects of rosuvastatin on atherosclerosis and cardiovascular morbidity and mortality.

Crisby M, Carlson LA, Winblad B. · The Alzheimer Disease Research Center, Karolinska Institute, Neurotec Division of Geriatric Medicine, Huddinge University Hospital, Stockholm, Sweden. · Alzheimer Dis Assoc Disord. · Pubmed #12218642 No free full text.

Abstract: Vascular risk factors such as hypertension and hypercholesterolemia during midlife increase the risk for Alzheimer's disease (AD). Treatment of hypercholesterolemia and other vascular risk factors may have great implications in the prevention of AD. Recent findings illustrate that the sterol metabolism in the brain is an active process, well controlled and regulated by 24-hydroxylase, an enzyme that is uniquely expressed in the brain. The use of statins in ischemic heart disease (IHD) has proven to be a phenomenal advance in pharmacological disease prevention and treatment. A growing body of evidence, suggest that statins exhibit additional benefits that are independent of their cholesterol-lowering actions. Statin treatment has also considerable effect in prevention of ischemic stroke. In animal models of ischemic stroke, statins have proven to reduce infarct size through up-regulation of endothelial nitric oxide synthases. Data from recent observational studies have revealed a potential role for statins in prevention of AD. The following review comments the processes leading to dementia including the involvement of cholesterol regulation, cerebral circulation and inflammation in development of dementia. The mechanisms by which statins may be beneficial in controlling these processes is discussed.

Camejo G, Olsson U, Hurt-Camejo E, Baharamian N, Bondjers G. · Wallenberg Laboratory for Cardiovascular Research, Sahlgrenska University Hospital, Gothenberg, Sweden. · Atheroscler Suppl. · Pubmed #12044579 No free full text.

Abstract: Atherosclerosis is remarkably increased in type 2 diabetes suggesting that mechanisms causing arterial lesion are enhanced by the metabolic disturbances of insulin resistance (IR) and diabetes. Several lines of research suggest that processes taking place in the arterial intima extracellular matrix may be part of a shared pathogenic mechanism. The intima extracellular matrix is where atherogenesis takes place. This layer contains fibrilar macromolecules like collagens, proteoglycans (PGs), hyaluronate, and extracellular multi-domain proteins. Specific interaction of lysine, arginine-rich segments of the apoB-100 lipoproteins, LDL, IDL and Lp (a), with the negatively charged glycosaminoglycans (GAGs) of PGs cause retention of the lipoproteins, one of the initiation process of atherogenesis. Such interactions cause structural modifications of the lipid and protein moieties of the lipoproteins that appear to increase their susceptibility to proteases, phospholipases and free radical-mediated processes. The association of apoB-lipoproteins, specially small and dense LDL, with intima PGs increases their uptake by macrophages and human arterial smooth muscle cells (HASMC) leading to 'foam cell' formation. In vitro, elevated levels of non-esterified fatty acids (NEFA) alter the matrix of endothelial cells basement membrane making them more permeable to macromolecules. NEFA cause changes in the expression of genes controlling the PGs composition of the PGs secreted by HASMC causing formation of a matrix with high affinity for LDL. These results lead us to speculate that an important component of the dyslipidemia of IR and type 2 diabetes, chronic high NEFA, may contribute to cellular alterations that cause changes of the arterial intima extracellular matrix. Such changes may increase the atherogenicity of the retention of apoB lipoproteins in the intima and contribute to the systemic alteration of the arterial wall frequently observed in IR and type 2 diabetes.

Lind L. · Department of Medicine, Uppsala University Hospital and AstraZeneca R&D, Möndal, Sweden. · Lipids. · Pubmed #11876256 No free full text.

Abstract: Studies using both in vitro and in vivo techniques have repeatedly shown that endothelium-dependent vasodilation (EDV) is impaired in different forms of experimental as well as human hypercholesterolemia. Clearly this impaired EDV can be reversed by lowering cholesterol levels by diet or medical therapy. Competitive blocking of L-arginine, changes in nitric oxide synthase activity, increased release of endothelin-1, and inactivation of nitric oxide due to superoxide ions all contribute to the impairment in EDV during dyslipidemia. The oxidation of low density lipoprotein, with its compound lysophosphatidylcholine, plays a critical role in these events. However, data on the role of triglycerides and fat-rich meals regarding EDV are not so consistent as data for cholesterol, although a view that the compositions of individual fatty acids and antioxidants are of major importance is emerging. Thus, this review shows that while impaired EDV is a general feature of hypercholesterolemia, the mechanisms involved and the therapeutic opportunities available still have to be investigated. Furthermore, discrepancies regarding the role of triglycerides and fat content in food may be explained by divergent effects of different fatty acids on the endothelium.

Melkersson K, Hulting AL. · Sollentuna sjukhus, Sollentuna. · Lakartidningen. · Pubmed #11769361 No free full text.

Abstract: Hormonally related side effects of antipsychotic drugs, e.g. weight gain, hyperlipidemia and diabetes have come to the forefront in that the use of clozapine and new antipsychotics have increased. Hormones involved are prolactin, growth hormone (GH), insulin-like growth factor I (IGF-I), insulin and leptin. Patients treated with clozapine had lower levels of GH-dependent IGF-I than patients receiving classical antipsychotics. Patients treated with olanzapine had higher serum insulin levels than those receiving classical antipsychotics, indicating a probable influence of olanzapine on insulin secretion. In clozapine-treated patients the insulin levels correlated to the clozapine serum concentration, indicating a likely influence also of clozapine on insulin secretion. The gender difference, i.e. that women normally have higher leptin levels than men, was found in patients receiving classical antipsychotics, but not in patients treated with clozapine or olanzapine.

Hellénius ML. · Centrum för klinisk hjärt-kärlforskning och Konung Gustaf V:s forskningsinstitut, Karolinska sjukhuset, Stockholm. · Lakartidningen. · Pubmed #11680152 No free full text.

This publication has no abstract.

Jönsson B. · Centre for Health Economics, Stockholm School of Economics, Box 6501, S-113 83, Stockholm, Sweden. · Lancet. · Pubmed #11675082 No free full text.

Abstract: Today's society places a great emphasis on value for money, so medical interventions must not only be shown to be effective but also be proved to be costeffective. Drug treatment is no exception. In health economics, costeffectiveness is calculated differently depending on the indication and the perspective. For cholesterol-lowering drugs (as an example) there is a difference between primary and secondary intervention. In primary prevention, the cut off value for absolute risk when treatment is costeffective varies with age and sex, but in secondary prevention, although treatment is costeffective for all groups of patients, costeffectiveness varies with age, sex, cholesterol concentration, and other risk factors. There are three complementary approaches to economic assessment of secondary prevention-analysis of the whole population, subgroup analysis, and modelling.

Bröijersén A, Wiklund B, Angelin B. · Centrum för metabolism och endokrinologi, Huddinge Universitetssjukhus. · Lakartidningen. · Pubmed #11586809 No free full text.

Abstract: In the new guidelines from the Swedish Medical Products Agency, an aggressive approach is recommended for the treatment of hyperlipidemia in all patients with manifest atherosclerotic disease. Patients with intermittent claudication should therefore receive lipid-lowering treatment on the same indications as patients with coronary artery disease. The present article reviews our knowledge of hyperlipidemia as a risk factor for the development of peripheral artery disease. Hyperlipidemia is frequently found in these patients and the most common lipid derangements are low levels of HDL-cholesterol and hypertriglyceridemia. Hard end-point data concerning morbidity and mortality during lipid-lowering treatment in this specific population is largely lacking, although previous studies indicate that lipid-lowering treatment slows the atherosclerotic process and induces pain relief.

Fellström B. · Uppsala University, Sweden. · Transplantation. · Pubmed #11583483 No free full text.

This publication has no abstract.

Olsson AG. · Clinical Research Center, University Hospital, Linköping, Sweden. · Clin Cardiol. · Pubmed #11501599 No free full text.

Abstract: Numerous studies have demonstrated that treatments designed to reduce low-density lipoprotein cholesterol (LDL-C) can reduce the risk of coronary heart disease (CHD) events in the setting of either primary or secondary prevention. The rationale for aggressive lowering of LDL-C, supported by large observational studies, is the concept that no threshold exists below which reductions fail to provide additional benefit. The statins are widely considered first-line therapy for preventing CHD events because these agents yield the greatest reductions in LDL-C. However, many patients do not achieve target LDL-C levels with the currently available statins. Newer, more effective statins may permit the benefits of aggressive LDL-C reduction to be extended to larger numbers of patients. A novel, highly efficacious statin, rosuvastatin (Crestor, AstraZeneca group of companies), is currently undergoing clinical investigation. Dose-ranging studies in hypercholesterolemic patients have shdwn that rosuvastatin produces significant, dose-dependent decreases in LDL-C when compared with placebo. Reductions have ranged from 34% at a dose of 1 mg/day to 65% at 80 mg/day. This agent has been found to be well tolerated across the range of doses studied. Phase III studies indicate that rosuvastatin is more effective than atorvastatin, pravastatin, and simvastatin in improving the atherogenic lipid profiles of hypercholesterolemic patients, and more effective than atorvastatin in improving the atherogenic lipid profiles of patients with heterozygous familial hypercholesterolemia. Overall, these findings suggest that rosuvastatin is a promising new medication for the treatment of dyslipidemias.

Groop L, Orho-Melander M. · Department of Endocrinology, Wallenberg Laboratory, Lund University, Malmö, Sweden. · J Intern Med. · Pubmed #11489060 No free full text.

Abstract: The first unifying definition for the metabolic syndrome was proposed by WHO in 1998. In accordance to this, patients with type 2 diabetes mellitus or impaired glucose tolerance have the syndrome if they fulfil two of the criteria: hypertension, dyslipidaemia, obesity/abdominal obesity and microalbuminuria. Persons with normal glucose tolerance (NGT) should also be insulin resistant. About 40% of persons with impaired glucose tolerance (IGT) and 70% of patients with type 2 diabetes have features of the syndrome. Importantly, presence of the dysmetabolic syndrome is associated with reduced survival, particularly because of increased cardiovascular mortality. The dysmetabolic syndrome most likely results from interplay between several genes and an affluent environment. Compatible with the thrifty gene theory, common variants in genes regulating lipolysis, thermogenesis and glucose uptake in skeletal muscle account for a large part of such thrifty genes. However, hitherto unknown genes may still be identified by random gene approaches.

Olsson AG. · Department of Medicine and Care, University Hospital, Linköping, Sweden. · Am J Cardiol. · Pubmed #11256849 No free full text.

Abstract: The utility of statins with increased potency in reducing low-density lipoprotein cholesterol (LDL-C) is indicated by evidence that aggressive LDL-C lowering is associated with increased reduction in coronary artery disease risk, and the need for such agents is illustrated by the fact that many patients currently fail to achieve LDL-C target levels during treatment with available drugs. In dose-ranging studies of patients with hypercholesterolemia, the new synthetic statin rosuvastatin (formerly ZD4522) produced significant, dose-dependent reductions in LDL-C compared with placebo across a range of doses. Reductions ranged from 34% at 1 mg per day to 65% at 80 mg per day, with linear regression analysis indicating an additional 4.5% reduction in LDL-C with each doubling of the rosuvastatin dose. Rosuvastatin treatment was well tolerated. Phase 3 clinical trials of this agent are under way.

Perk J, Veress G. · Department of Internal Medicine and Rehabilitation, Oskarshamn Hospital, Sweden. · Eur J Appl Physiol. · Pubmed #11138589 No free full text.

Abstract: In this paper new insights into the beneficial effects of physical training for patients with coronary artery disease are reviewed. Endurance training as part of a comprehensive cardiac rehabilitation programme in combination with strength training, smoking cessation and lipid management may slow down and in some cases reverse the progress of coronary atherosclerosis. Thus, exercise training remains an invaluable tool in the hands of the clinical cardiologist dealing with chronic coronary care.

Hansson GK. · Center for Molecular Medicine, Karolinska HospitalKarolinska Institutet, SE-17176 Stockholm, Sweden. · Curr Atheroscler Rep. · Pubmed #11122704 No free full text.

Abstract: Atherosclerosis is an inflammatory disease with a significant autoimmune component. Studies using transgenic murine models have clarified that recruitment of mononuclear leukocytes through vascular leukocyte-adhesion molecules and chemokines, differentiation of monocytes to macrophages, and endocytosis through scavenger receptors all are of decisive importance for atherosclerosis in hypercholesterolemic mice. T and B cells modulate disease progression and lesion development is reduced in mice lacking adaptive immunity. In particular, local immune responses eliciting Th1 effector mechanisms appear to be proatherogenic, whereas protective immune responses can be induced by immunization with oxidized low-density lipoprotein. Thus, innate immunity is necessary for atherosclerosis, whereas adaptive immunity is an important modulator of disease development.

Holm C, Osterlund T, Laurell H, Contreras JA. · Department of Cell and Molecular Biology, Section for Molecular Signalling, Lund University, Lund, Sweden. · Annu Rev Nutr. · Pubmed #10940339 No free full text.

Abstract: Hormone-sensitive lipase, the rate-limiting enzyme of intracellular TG hydrolysis, is a major determinant of fatty acid mobilization in adipose tissue as well as other tissues. It plays a pivotal role in lipid metabolism, overall energy homeostasis, and, presumably, cellular events involving fatty acid signaling. Detailed knowledge about its structure and regulation may provide information regarding the pathogenesis of such human diseases as obesity and diabetes and may generate concepts for new treatments of these diseases. The current review summarizes the recent advances with regard to hormone-sensitive lipase structure and molecular mechanisms involved in regulating its activity and lipolysis in general. A summary of the current knowledge regarding regulation of expression, potential involvement in lipid disorders, and role in tissues other than adipose tissue is also provided.

Hansson GK, Zhou X, Törnquist E, Paulsson G. · Karolinska Institutet, Center for Molecular Medicine, Karolinska Hospital, Stockholm, Sweden. · Ann N Y Acad Sci. · Pubmed #10865825 No free full text.

Abstract: Atherosclerosis is an inflammatory disease induced by a lipid metabolic disturbance at sites of hemodynamic strain in the vasculature. Studies in both man and experimental animal models show an involvement of innate and adaptive immune mechanisms in the disease process. Our recent studies in apoE-knockout mice show that the level of hypercholesterolemia affects the functional properties of the immune response. Modulating immune activity by injections of polyclonal immunoglobulins inhibits disease progression, suggesting that immunomodulation may be useful to treat atherosclerosis. Analysis of T cell receptor (TCR) mRNA in atherosclerotic lesions shows expansions of T cells expressing TCR-V beta 6, a receptor type that is also expressed by T cells recognizing oxidized low density lipoprotein (oxLDL). This suggests that oxLDL is an autoantigen that induces strong, local T cell responses in the plaque. Further characterization of this and other candidate antigens, such as heat shock proteins and macromolecular components of Chlamydia pneumoniae, may provide important information on which specific interference with the disease process could be based.

Björntorp P, Holm G, Rosmond R, Folkow B. · Department of Heart and Lung Disease, University of Göteborg, Sweden. · Blood Press. · Pubmed #10855728 No free full text.

Abstract: In primary hypertension a mild hyperresponsiveness of hypothalamic, sympatho-hormonal centres to psychosocial stimuli forms a major pathogenetic element, although high salt intake in some subjects may contribute via volume expansion. Hypertension is often associated with another "civilisation" disorder, the metabolic syndrome, defined as abdominal obesity, insulin resistance and dyslipidaemia. According to recent research, the metabolic syndrome has in all likelihood a central neuroendocrine origin in the form of enhanced engagement of the hypothalamic-pituitary-adrenal (HPA) axis. Here the peripheral endocrine perturbations act as triggers for both central obesity and the metabolic abnormalities. The reaction pattern characterising early primary hypertension is identical with, or closely related to, the "defence reaction", while that leading to the metabolic syndrome is similar to that of the "defeat reaction". Both belong to the primitive survival reactions, common to all mammals, though man can control, or at least mask, his outward-behavioural part but not the neuro-hormonal expressions. Animal experiments show how frequent or chronic mental challenges are capable of engaging these limbic-hypothalamic centres, affecting blood pressure regulation as well as endocrine-metabolic regulation. Furthermore, these centres are tightly coupled functionally, and their signals to the periphery often combined. On a long-term basis their engagements appear to be decisive for the development of both primary hypertension and the metabolic syndrome, as suggested by intervention studies. In both these "disorders of civilisation", observations strongly indicate that psychosocial stress, socioeconomic handicaps, lack of exercise, abuse and also psychiatric traits are involved. Such factors, characteristic of current competitive society, probably cause mixed engagements of the two above-mentioned neuro-hormonal patterns, and thereby, with time, primary hypertension and the metabolic syndrome, with end-points such as coronary artery disease, diabetes mellitus type2 and stroke. Susceptibility to such developments is probably enhanced by genetic factors. This overview of recent developments therefore serves to emphasise how both primary hypertension and the metabolic syndrome seem to have a common central origin. Central regulatory factors are often overlooked, partly because it is not realised that limbic-hypothalamic centres are the major regulators of both circulatory and metabolic events, and partly because of the long period of time required before these disease end-points are reached.

Fellström B. · Department of Medical Sciences, University Hospital, Uppsala, Sweden. · Transplant Proc. · Pubmed #10576035 No free full text.

This publication has no abstract.

Angelin B, Eriksson M, Rudling M. · Department of Medicine, Karolinska Institutet at Huddinge University Hospital, Sweden. · Curr Opin Lipidol. · Pubmed #10431663 No free full text.

Abstract: Based on an improved molecular understanding of how bile acid metabolism is regulated, an exciting period of research developments can be expected. By new ways of stimulating cholesterol breakdown to bile acids, novel therapeutic principles can be forseen which will further improve our potential for treating and preventing atherosclerosis.

Sjöström L, Lindroos AK, Peltonen M, Torgerson J, Bouchard C, Carlsson B, Dahlgren S, Larsson B, Narbro K, Sjöström CD, Sullivan M, Wedel H, Anonymous00288. · Department of Body Composition and Metabolism, Sahlgrenska University Hospital, Göteborg, Sweden. · N Engl J Med. · Pubmed #15616203 links to  free full text

Abstract: BACKGROUND: Weight loss is associated with short-term amelioration and prevention of metabolic and cardiovascular risk, but whether these benefits persist over time is unknown. METHODS: The prospective, controlled Swedish Obese Subjects Study involved obese subjects who underwent gastric surgery and contemporaneously matched, conventionally treated obese control subjects. We now report follow-up data for subjects (mean age, 48 years; mean body-mass index, 41) who had been enrolled for at least 2 years (4047 subjects) or 10 years (1703 subjects) before the analysis (January 1, 2004). The follow-up rate for laboratory examinations was 86.6 percent at 2 years and 74.5 percent at 10 years. RESULTS: After two years, the weight had increased by 0.1 percent in the control group and had decreased by 23.4 percent in the surgery group (P<0.001). After 10 years, the weight had increased by 1.6 percent and decreased by 16.1 percent, respectively (P<0.001). Energy intake was lower and the proportion of physically active subjects higher in the surgery group than in the control group throughout the observation period. Two- and 10-year rates of recovery from diabetes, hypertriglyceridemia, low levels of high-density lipoprotein cholesterol, hypertension, and hyperuricemia were more favorable in the surgery group than in the control group, whereas recovery from hypercholesterolemia did not differ between the groups. The surgery group had lower 2- and 10-year incidence rates of diabetes, hypertriglyceridemia, and hyperuricemia than the control group; differences between the groups in the incidence of hypercholesterolemia and hypertension were undetectable. CONCLUSIONS: As compared with conventional therapy, bariatric surgery appears to be a viable option for the treatment of severe obesity, resulting in long-term weight loss, improved lifestyle, and, except for hypercholesterolemia, amelioration in risk factors that were elevated at baseline.