Haptoglobin genotype 2-2 associated with atherosclerosis in patients with ischemic stroke.

AIM: Ischemic stroke (IS) is multifactorial disease and therefore different genes and proteins play a role in its development. Haptoglobin (Hp) removes free hemoglobin and protects from iron-induced oxidative damage, inflammatory response, atherosclerosis and cerebrovascular diseases. The aim of this study was to investigate Hp genetic variants in patients with carotid atherosclerotic lesions and IS. MATERIAL AND METHODS: A total of 121 subjects with IS participated in the study, 81 male and 40 female. RESULTS: Among 121 patients with IS, 79 had diffuse atherosclerotic plaques and stenosis. Hp genotype was statistically significantly associated with CDFI neck carotid artery stenosis findings (p = 0.006). Patients with Hp1-2 genotype had statistically significantly larger odds for atherosclerotic changes compared to those with Hp1-1 genotype, as well as those with Hp2-2 genotype. CONCLUSION: This study has shown an association of the Hp2-2 genotype and atherosclerosis in patients with IS, indicating Hp2-2 genotype as a genetic biomarker for precision medicine and personalized healthcare.

Guidelines for the prevention, detection and therapy of vitamin d deficiency in adults

It is estimated that over one billion of people around the globe have low serum values of vitamin D, therefore, we can consider vitamin D deficiency as a pandemic and public health problem. Geographic position of Croatia, especially the continental part of the country, is a risk factor for the development of deficiency of vitamin D in the population. The aim of these guidelines is to provide the clinicians with easy and comprehensive tool for prevention, detection and therapy of vitamin D deficienney in healthy population and various groups of patients. They were made as a result of collaboration of clinicians of different backgrounds who are dealing with patients at risk of vitamin D deficiency. These guidelines are evi- dence-based, according to GRADE-system (Grading of Recommendations, Assessment, Development and Evaluation), which describes the level of evidence and strength of recommendation. The main conclusions address the recommended serum vitamin D values in the population which should be between 75 and 125 nmol/L and defining recommended preven- tive and therapeutic dosages of vitamin D in order to reach the adequate levels of serum vitamin

Lipid lowering drug therapy in patients with coronary heart disease from 24 European countries--Findings from the EUROASPIRE IV survey.

OBJECTIVE: Since dyslipidaemia is one of the most important risk factors for coronary heart disease (CHD), lowering of LDL-cholesterol (LDL-C) causes significant reduction in morbidity and mortality, particularly in patients with established CHD. The aim of this survey was to assess how statins were prescribed in CHD patients at discharge after a coronary event from hospitals throughout Europe and how the intake of these drugs was reported by the patients when they were seen more than one year later in relationship with their achieved LDL-C levels. METHODS: 6648 CHD patients' data from centres in 24 European countries were gathered using standardized methods. Lipid measurements were performed in one central laboratory. Patients were divided in three groups: high-intensity statin therapy, moderate or low intensity statin therapy and no statin therapy at all. RESULTS: 90.4% CHD patients were on statin therapy at the time of discharge from the hospital which decreased to 86% one year later. Only 37.6% of these patients were prescribed a high-intensity statin at discharge which even decreased to 32.7% later. In only 6 countries (all of them high-income countries) the number of patients on a high-intensity statin therapy increased substantially after the hospital discharge. It is worrying that statin therapy was discontinued in 11.6% and that only 19.3% of all CHD patients achieved target values of LDL-C < 1.8 mmol/L at the time of interview. CONCLUSIONS: Too many CHD patients with dyslipidaemia are still inadequately treated and most of these patients on statin therapy are not achieving the treatment targets. Therapeutic control of LDL-C is clearly related to the intensity of lipid lowering drug regimen after the CHD event indicating that a considerable potential still exists throughout Europe to reduce CHD mortality and morbidity rates through more efficient LDL-C lowering.

Alirocumab: targeting PCSK9 to treat hypercholesterolemia.

Lowering of low-density lipoprotein (LDL) cholesterol reduces coronary heart disease morbidity and mortality, not only in secondary but also in primary prevention. Statins are generally accepted as a treatment of choice for this. However, still many high-risk and very-high-risk patients fail to achieve target LDL cholesterol values. Therefore, a new class of lipid-lowering drugs was recently developed-inhibitors of proprotein convertase subtilisin/kexin type 9 (PCSK9). Alirocumab was the first drug in this class to be approved by the U.S. Food and Drug Administration (FDA) and recently also by the European Medicines Agency (EMA). Alirocumab has been shown to lower LDL cholesterol by up to 60% with a safety profile comparable to that of placebo. Large outcome studies are still on the way and their first results will be available in 2017. This review focuses on alirocumab, discussing currently available hard evidence on the beneficial effects of this drug in the treatment of hypercholesterolemia.

Resistance and intolerance to statins.

BACKGROUND AND AIMS: Many patients treated with statins are considered statin-resistant because they fail to achieve adequate reduction of low density lipoprotein cholesterol (LDL-C) levels. Some patients are statin-intolerant because they are unable to tolerate statin therapy at all or to tolerate a full therapeutic statin dose because of adverse effects, particularly myopathy and increased activity of liver enzymes. RESULTS: The resistance to statins has been associated with polymorphisms in the 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA-R), P-glycoprotein (Pg-P/ABCB1), breast cancer resistance protein (BCRP/ABCG2), multidrug resistance-associated proteins (MRP1/ABCC1 and MRP2/ABCC2), organic anion transporting polypeptides (OATP), RHOA, Nieman-Pick C1-like1 protein (NPC1L1), farnesoid X receptor (FXR), cholesterol 7alpha-hydroxylase (CYP7A1), Apolipoprotein E (ApoE), proprotein convertase subtilisin/kexin type 9 (PCSK9), low density lipoprotein receptor (LDLR), lipoprotein (a) (LPA), cholesteryl ester transfer protein (CETP), and tumor necrosis factor α (TNF-α) genes. However, currently, there is still not enough evidence to advocate pharmacogenetic testing before initiating statin therapy. Patients with inflammatory states and HIV infection also have diminished LDL-C lowering as a response to statin treatment. Pseudo-resistance due to nonadherence or non-persistence in real-life circumstances is probably the main cause of insufficient LDL-C response to statin treatment. CONCLUSIONS: If a patient is really statin-resistant or statin-intolerant, several other treatment possibilities are nowadays available: ezetimibe alone or in combination with bile acid sequestrants, and possibly in the near future mipomersen, lomitapide, or monoclonal antibodies against PCSK9.

SURF - SUrvey of Risk Factor management: first report of an international audit.

BACKGROUND: Despite the fact that subjects with established coronary heart disease (CHD) are at high risk of further events and deserve meticulous secondary prevention, current audits such as EUROASPIRE show poor control of major risk factors. Ongoing monitoring is required. We present a new risk factor audit system, SURF (Survey of Risk Factor management), that can be conducted much more quickly and easily than existing audit systems and has the potential to allow hospitals of all sizes to participate in a unified international audit system that will complement EUROASPIRE. Initial experience indicates that SURF is truly simple to undertake in an international setting, and this is illustrated with the results of a substantive pilot project conducted in Europe and Asia. METHODS: The data collection system was designed to allow rapid and easy data collection as part of routine clinic work. Consecutive patients (aged 18 and over) with established CHD attending outpatient cardiology clinics were included. Information on demographics, previous coronary medical history, smoking history, history of hypertension, dyslipidaemia or diabetes, physical activity, attendance at cardiac rehabilitation, cardiac medications, lipid and glucose levels (and HbA1c in diabetics) if available within the last year, blood pressure, heart rate, body mass index, and waist circumference were collected using a one-page data collection sheet. Years spent in full time education was added as an additional question during the pilot phase. RESULTS: Three European countries - Ireland (n = 251), Belgium (n = 122), and Croatia (n = 124) - and four Asian countries - Singapore (n = 142), Taiwan (n = 334), India (n = 97), and Korea (n = 45) - were included in the pilot study. The results of initial field testing were confirmed in that it proved possible to collect data within 60-90 seconds per subject. There was poor control of several risk factors including high levels of physical inactivity (41-45%), overweight and obesity (59-78%), and ongoing smoking (15%). There were lower levels of individuals attending cardiac rehabilitation in Asia. More Europeans than Asians reached the low-density lipoprotein cholesterol target of <2.5 mmol/l (66 vs. 59%) reflecting differences in medication usage. However, blood pressure control was superior in Asia, with 71% <140/90 compared with 66% of Europeans (NS). CONCLUSIONS: This phase of SURF has confirmed its ease of use which should allow wide participation and the collection of representative risk factor data in subjects with CHD as well as ongoing data collection to monitor secular trends in risk factor control. Notwithstanding that this is a pilot study, the results suggest that risk factor control, particularly for lifestyle-related measures, is poor in both Europe and Asia.

Managing the residual cardiovascular disease risk associated with HDL-cholesterol and triglycerides in statin-treated patients: a clinical update.

Cardiovascular disease (CVD) is a significant cause of death in Europe. In addition to patients with proven CVD, those with type 2 diabetes (T2D) are at a particularly high-risk of CVD and associated mortality. Treatment for dyslipidaemia, a principal risk factor for CVD, remains a healthcare priority; evidence supports the reduction of low-density lipoprotein cholesterol (LDL-C) as the primary objective of dyslipidaemia management. While statins are the treatment of choice for lowering LDL-C in the majority of patients, including those with T2D, many patients retain a high CVD risk despite achieving the recommended LDL-C targets with statins. This 'residual risk' is mainly due to elevated triglyceride (TG) and low high-density lipoprotein cholesterol (HDL-C) levels. Following statin therapy optimisation additional pharmacotherapy should be considered as part of a multifaceted approach to risk reduction. Fibrates (especially fenofibrate) are the principal agents recommended for add-on therapy to treat elevated TG or low HDL-C levels. Currently, the strongest evidence of benefit is for the addition of fenofibrate to statin treatment in high-risk patients with T2D and dyslipidaemia. An alternative approach is the addition of agents to reduce LDL-C beyond the levels attainable with statin monotherapy. Here, addition of fibrates and niacin to statin therapy is discussed, and novel approaches being developed for HDL-C and TG management, including cholesteryl ester transfer protein inhibitors, Apo A-1 analogues, mipomersen, lomitapide and monoclonal antibodies against PCSK9, are reviewed.

Importance of characteristics and modalities of physical activity and exercise in the management of cardiovascular health in individuals with cardiovascular risk factors: recommendations from the EACPR. Part II.

In a previous paper, as the first of a series of three on the importance of characteristics and modalities of physical activity (PA) and exercise in the management of cardiovascular health within the general population, we concluded that, in the population at large, PA and aerobic exercise capacity clearly are inversely associated with increased cardiovascular disease risk and all-cause and cardiovascular mortality and that a dose­response curve on cardiovascular outcome has been demonstrated in most studies. More and more evidence is accumulated that engaging in regular PA and exercise interventions are essential components for reducing the severity of cardiovascular risk factors, such as obesity and abdominal fat, high BP, metabolic risk factors, and systemic inflammation. However, it is less clear whether and which type of PA and exercise intervention (aerobic exercise, dynamic resistive exercise, or both) or characteristic of exercise (frequency, intensity, time or duration, and volume) would yield more benefit for each separate risk factor. The present paper, therefore, will review and make recommendations for PA and exercise training in the management of cardiovascular health in individuals with cardiovascular risk factors. The guidance offered in this series of papers is aimed at medical doctors, health practitioners, kinesiologists, physiotherapists and exercise physiologists, politicians, public health policy makers, and individual members of the public. Based on previous and the current literature overviews, recommendations from the European Association on Cardiovascular Prevention and Rehabilitation are formulated regarding type, volume, and intensity of PA and regarding appropriate risk evaluation during exercise in individuals with cardiovascular risk factors.

Development of a high-resolution melting method for mutation detection in familial hypercholesterolaemia patients.

AIMS: Current screening methods, such as single strand conformational polymorphism (SSCP) and denaturing high performance liquid chromatography (dHPLC) that are used for detecting mutations in familial hypercholesterolaemia (FH) subjects are time consuming, costly and only 80-90% sensitive. Here we have tested high-resolution melt (HRM) analysis for mutation detection using the Rotor-Gene(6000) realtime rotary analyser. Methods and subjects Polymerase chain reaction and melt conditions (HRM) for 23 fragments of the LDL-receptor gene, a region of exon 26 in the APOB gene (including p.R3527Q) and exon 7 of the PCSK9 gene (including p.D374Y) were optimized. Two double stranded DNA saturating dyes, LC-Green and Syto9, were compared for sensitivity. Eighty-two samples with known mutations were used as positive controls. Twenty-eight Greek FH heterozygous patients and two homozygous patients from the UK and Croatia were screened. RESULTS: HRM was able to identify all the positive control mutations tested, with similar results with either dye. Eight different variations were found in 17 of the 28 Greek FH patients for an overall detection rate of 61%: c.41delT (1), p.W165X (1), p.C173R (3), p.S286R (2), p.V429M (4), p.G549D (4), p.V613I (1), and a previously unreported mutation p.F694V (1) which is predicted to be FH-causing by functional algorithms. Mutations were found in both the homozygous patients; p.Q92X (Croatia) and p.Y489C (UK); both patients were homozygous for their respective mutations. CONCLUSIONS: HRM is a sensitive, robust technique that could significantly reduce the time and cost of screening for mutations in a clinical setting.

Renal transplantation in patients with Balkan endemic nephropathy.

BACKGROUND: Balkan endemic nephropathy (BEN) is a chronic tubulointerstitial disease prevalent in Croatia, Romania, Bulgaria, Bosnia and Herzegovina, and Serbia. In addition to renal disease, an increased incidence of upper urothelial carcinomas (UUCs) has been observed in the foci of BEN. Carcinoma may occur alone or in combination with BEN. Immunosuppression is associated with an increased risk for development of different malignancies. There are no data in the literature about the outcome of patients with BEN after transplantation. METHODS: We performed a retrospective evaluation of the database and review of the charts and pathology reports of 601 renal transplant recipients treated at our institution. RESULTS: From January 1995 to December 2004, kidney transplantations were performed in nine patients with BEN. One-year graft survival was 100%. A man, who was transplanted in 1997 died 2 years after transplantation with a functioning graft due to disseminated cancer from the pelvis of his own kidney. A female patient developed UCC 2 years after transplantation. They were both treated with a bolus of methylprednisolone before transplantation, because of four HLA-mismatches. A male patient developed UCC in the native and transplanted kidneys. He underwent a native nephroureterectomy with partial nephroureterectomy of transplanted kidney. His graft function was preserved with decreased immunosuppression. Three years later a urinary bladder carcinoma was discovered on a regularly performed multislice computed tomography. One patient developed a skin malignancy. Other patients have had uneventful posttransplantation courses with excellent graft function. Thus, 33.3% of patients with BEN developed UUC, compared with a 0.67% prevalence of urinary tract tumors among transplanted patients with other causes of end-stage renal disease. CONCLUSION: Patients with BEN are at increased risk for the development of UCC after transplantation. Regular screening for early detection of malignancy is mandatory. Longer follow-up and results from other transplant centers are needed to further investigate the relationship between BEN and UCC after renal transplantation.

Is lipoprotein(A) a risk factor for atherosclerosis of the retinal arteries?

Elevated plasma Lp(a) has been linked to development of coronary artery disease (CAD). There is no data about plasma Lp(a) and atherosclerosis of the retinal arteries. Therefore the purpose of this study was to assess the risk of retinal vessels atherosclerosis conferred by elevated plasma Lp(a) levels in 73 adult males. The results were compared with those in 45 matched apparently healthy males with no retinal vessel changes. The atherosclerotic changes of the retinal vessels were determined by direct ophthalmoscopy and graded (1-4) according to Scheie. Plasma levels of Lp(a) were measured by radial immunodiffusion. The results were compared using chi-square test. Although a very weak correlation between plasma Lp(a) levels and the incidence of retinal atherosclerosis was found, no significant association between the degree of atherosclerotic changes and plasma Lp(a) levels could be proven. Thus it could be concluded that plasma Lp(a) level is not a significant risk factor for atherosclerosis of the retinal arteries.

Plasma cortisol in men--relationship with atherosclerosis of retinal arteries.

The production of cortisol increases in acute stress but the effects of chronic stress on plasma cortisol are still controversial. Stress on the other hand plays a role in coronary artery disease (CAD) and carotid atherosclerosis. Since there is no data about plasma cortisol and atherosclerosis of the retinal arteries, the purpose of this study was to explore the relationship between plasma cortisol in 101 adult males with the degree of their retinal vessels atherosclerosis. The results were compared with those in 47 matched apparently healthy men with no retinal vessels changes. The atherosclerotic changes of retinal vessels were determined by direct ophthalmoscopy and graded (1-4) according to Scheie. Morning plasma cortisol levels were determined by radioimmunoassay using commercial kits. The results were compared by using chi-square test. No association between morning plasma cortisol concentrations and retinal vessels atherosclerosis could be found. The results of this study do not support a role for physiological levels of plasma cortisol in the development of atherosclerosis, at least of the retinal arteries, in men.

[Estrogens and risks for onset of atherosclerosis]. / Estrogeni i rizik nastanka ateroskleroze.

There are many evidences suggesting that estrogens prevent atherosclerosis and its consequences such as coronary heart disease (CHD) in women. The risk for CHD is less in premenopausal women when compared with age-matched men, but the protective effect of estrogens is lost with menopause. A part of this beneficial effect may be ascribed to the ability of estrogens to favorably alter the plasma lipoproteins profile, i.e. increase HDL and decrease LDL and Lp(a). However, the changes in the lipid profile do not fully account for the protective effect afforded by estrogens, indicating that other mechanisms are likely to be involved. One of these mechanisms may include estrogens ability to prevent oxidative modification of LDL. A number of animal and human studies strongly suggest also a direct effect on the vascular endothelium, decreasing the expression of adhesion molecules involved in monocyte adhesion such as VCAM-1. It seems that estrogens also cause by increasing the synthesis of NO a decrease in chemokines involved in monocyte migration into the subendothelial space (TNF alpha, IL-1 and MCP-1) and growth factors influencing the migration of smooth muscle cells (PDGF). They also decrease fibrinogen and homocysteine, and these substances when increased are considered independent risk factors for CHD. However, the results of the first randomised controlled trial of hormone replacement therapy (HRT) with estrogens concerning the CHD published recently differ from previous observational epidemiological studies in both primary and secondary intervention, which showed beneficial effect of HRT. The final answer about the effects of HRT on CHD is expected from several ongoing trials.

[New information on the pathophysiology of atherosclerosis]. / Novije spoznaje o patofiziologiji ateroskleroze.

The past decade has witnessed enormous progress in our understanding of the nature of this process. The development of an atherosclerotic plaque is a complex process which begins with endothelial dysfunction, the trigger for which are factors such as hypercholesterolemia, smoking, hypertension, hyperhomocysteinemia and impaired glucose metabolism. This dysfunction includes increased endothelial permeability to lipoproteins and other plasma constituents, which is mediated by NO, PDGF, prostacyclin, angiotensin II and endothelin; up-regulation of endothelial adhesion molecules including VCAM-1, ICAM-1, and selectins and migration of leukocytes and monocytes-macrophages in the subendothelial space mediated by oxidized LDL, MCP-1, PDGF and MCSF. The next step includes smooth-muscle cells migration (stimulated by PDGF and TGF-beta), T-cell activation (mediated by TNF-alpha and IL-2), formation of foam-cells from macrophages (mediated by oxidized LDL, MCSF, TNF-alpha and IL-1) and platelet adherence and aggregation (stimulated by thromboxane A2, tissue factor etc). The smooth muscle cells form a fibrous cap which confers mechanical stability of the plaque and separates the lipid rich thrombogenic core from the lumen and circulating blood. Whether a plaque will remain intact and therefore stable or rupture and lead to thrombosis causing an acute coronary syndrome (MI, unstable angina pectoris) depends upon a number of factors, the most important of which is its composition. Plaque size plays only a minor role in determining risk of an acute coronary syndrome. Rupture of the fibrous cap occurs due to thinning of the cap caused by an influx and activation of macrophages which release metalloproteinases and other proteolytic enzymes (stimulated by inflammatory cells, particularly T-lymphocytes). These enzymes cause degradation of the fibrous tissue of the cap which can result in thrombous formation and occlusion of the artery. Stable plaques have a thick fibrous cap, a small lipid core, and few inflammatory cells. In contrast, vulnerable plaques have a high lipid content, numerous inflammatory cells, and a thin fibrous cap with reduced collagen and vascular smooth muscle cells in it. Although vulnerable plaques are believed to account for only a small number of all coronary atheromas, they are responsible for most acute coronary events.

Effect of simvastatin on micropulmonary red cell mass in patients with hyperlipoproteinemia.

The purpose of this study was to compare the macrocirculatory and microcirculatory effects of simvastatin in hyperlipemic patients. In vitro measurements of lipoprotein levels and macrocirculatory hemorheology were complemented by in vivo measurements of the pulmonary capillary red cell volume (RCVpc) before and after 6 weeks of treatment with 40 mg of simvastatin daily in 30 male patients with hyperlipoproteinemia type IIa. RCVpc was assessed from the vascular component of the lung diffusing capacity for carbon monoxide, using the modification of the Roughton-Forster's method. RCVpc was increased in patients (60.9+/-9 versus 40+/-9 ml in healthy controls) and it decreased to 47+/-6 ml after treatment (P=5x10(-11)). The decreases in RCVpc correlated to concomitant decreases in peripheral hematocrit (R=0.68) and serum total cholesterol (-34% on average; R=0.59). Membrane diffusing capacity was normal in patients and not affected by the therapy; suggesting that increased RCVpc was due to increased micropulmonary hematocrit. Thus, it appears that viscosity in microcirculation is greatly increased in hyperlipemic patients and that simvastatin is able to normalize it. Since microcirculatory conditions can only partly be inferred from in vitro measurements the use of lung diffusional parameters was advocated, which enable in vivo assessment of hemorheology in microcirculation.

[Presence of Chlamydia pneumoniae antibodies in patients with ischemic heart disease and acute myocardial infarct]. / Nazocnost protutijela protiv Chlamydia pneumoniae u bolesnika s ishemicnom bolesti srca i akutnim infarktom miokarda.

Numerous seroepidemiological studies that suggest an association of C. pneumoniae infection and atherosclerosis have been published in last decade. The aim of this study was to assess a prevalence of C. pneumoniae antibodies in population of Zagreb area, and to investigate possible differences in prevalence of antibodies in patients with atherosclerosis and healthy controls. Forty-seven patients with coronary artery disease or myocardial infarction and 54 controls without any previous history of atherosclerosis were enrolled in the study. Sera were examined by microimmunofluorescence test. Persons with IgA antibody titers > or = 1:32, and/or IgG antibody titers > or = 1:64 were considered as seropositive. We found 75% seropositive in a total number of subjects, although number of seropositive and higher titers of antibodies were found more often in patients with atherosclerosis compared to control group: 74.5% of IgA seropositive patients versus 33.3% seropositive in control group, and 89.4% of IgG seropositive patients compared to 63% seropositive controls. Chronic (persistent) infections with C. pneumoniae were noted in 74.5% of patients and 33.3% controls.

Plasma lipids, lipoprotein Lp(a), apolipoproteins, and hemostatic risk factors distributions in postmenopausal women.

In the present study, the effect of hormone replacement therapy on lipid metabolism, apolipoproteins and hemostatic risk factors for cardiovascular disease was assessed in 216 Croatian postmenopausal women. There were 156 current users divided in to two groups according to the duration of therapy. The short-term study of < 10 months (X +/- SD 5.31 +/- 2.69) included 49 users, and long-term study of > 11 months (X +/- SD 22.06 +/- 10.95) included 107 users of hormone replacement therapy. Sixty nonusers served as a control group. In the short-term study, current users had a significant increase in serum HDL cholesterol, apolipoprotein A-I, A-II and a decrease in total/HDL cholesterol ratio, apoB and antithrombin III (p < 0.05). No significant differences were recorded for total cholesterol, triglycerides, LDL cholesterol, lipoprotein Lp(a) and plasminogen. In the long-term study, a significant increase in HDL cholesterol, apo A-I and total/HDL cholesterol ratio, and a decrease in AT III were observed. Results of the study showed favorable effects of hormone replacement therapy on serum lipid profile and apolipoproteins as a protective regimen from cardiovascular disease in both treatment groups of postmenopausal women. There are conflicting reports regarding increased fibrinolytic activity. The clinical relevance of the observed changes in antithrombin III concentrations as an important coagulation inhibitor is doubtful and should be considered in a more extensive evaluation of the potential hemostatic risk factors for cardiovascular risk and thromboembolism.

Extracorporeal treatment for refractory hyperlipidemia.

Radical, non-pharmacological, methods of treatment should never be used until it has first been shown that conventional therapy either fails to control hyperlipidemia or cannot be tolerated by the patient. In general, the use of extracorporeal techniques will be restricted to patients with severe familial hypercholesterolemia, although occasionally they may be resorted to in other categories of hyperlipidemia. Seven different procedures are available today for routine clinical practice: unselective plasma exchange, semi-selective double filtration and its modifications as well as the highly selective procedures of immunoadsorption, chemo-adsorption onto dextran sulfate, heparin induced LDL precipitation lipoprotein(a) column, and LDL hemoperfusion (direct adsorption of lipids--DALI). Large-scale regression studies were performed with five highly selective treatment modalities. Control coronary angiograms obtained after about two years of treatment showed that atherosclerotic plaques on coronary arteries had not enlarged or had even been reduced in 80% to 90% of patients.