Achieving National Cholesterol Education Program goals for low-density lipoprotein cholesterol in cardiac patients: importance of diet, exercise, weight control, and drug therapy.

OBJECTIVE: To determine how frequently the National Cholesterol Education Program (NCEP) goal of a low-density lipoprotein (LDL) cholesterol level of 100 mg/dL or less is achieved in clinical practice in patients with coronary artery disease and what fraction of patients can achieve this goal without drug therapy. DESIGN: We examined the results of lipid management in 152 consecutive patients who had completed cardiac rehabilitation after an acute coronary event. Patients were randomized to follow-up by specially trained nurses or by preventive cardiologists, and they were not receiving lipid-lowering drugs at the start of the study. MATERIAL AND METHODS: Patients were given aggressive diet and exercise recommendations and lipid-lowering drugs in accordance with NCEP guidelines. Follow-up was continued for a mean of 526 days after the first lipid assessment subsequent to the coronary event. Multiple logistic regression analysis was used to identify independent predictors of a final LDL cholesterol level of 100 mg/dL or less. RESULTS: Of the study group, 39% achieved the NCEP goal LDL cholesterol level of 100 mg/dL or less. Characteristics of the patients with LDL cholesterol levels of 100 mg/dL or less in comparison with those with LDL cholesterol levels of more than 100 mg/dL included a greater frequency of drug therapy (65% versus 38%), more rigorous dietary compliance, longer follow-up (586 +/- 317 days versus 493 +/- 264 days), more favorable weight change (-0.3 +/- 4.9 kg versus +1.7 +/- 5.0 kg), and more extensive weekly exercise (183 +/- 118 minutes versus 127 +/- 107 minutes). CONCLUSION: The registered nurses managed the lipids of these patients as effectively as did the preventive cardiologists. Appropriate drug therapy was the most important factor in achieving an LDL cholesterol level of 100 mg/dL or less, but 35% of patients attaining this NCEP goal were not receiving drug therapy. Exercise, dietary compliance, and weight loss were also important factors.     

First steps toward the establishment of a German low-density lipoprotein-apheresis registry: recommendations for the indication and for quality management.

New recommendations for the indication of treatment with selective extracorporeal plasma therapy low-density lipoprotein apheresis (LDL-apheresis) in the prevention of coronary heart disease are urgently needed. The following points are the first results of the ongoing discussion process for indications for LDL-apheresis in Germany: all patients with homozygous familial hypercholesterolemia with functional or genetically determined lack or dysfunction of LDL receptors and plasma LDL cholesterol levels >13.0 mmol/L (>500 mg/dL); patients with coronary heart disease (CHD) documented by clinical symptoms and imaging procedures in which over a period of at least 3 months the plasma LDL cholesterol levels cannot be lowered below 3.3 mmol/L (130 mg/dL) by a generally accepted, maximal drug-induced and documented therapy in combination with a cholesterol-lowering diet; and patients with progression of their CHD documented by clinical symptoms and imaging procedures and repeated plasma Lp(a) levels >60 mg/dL, even if the plasma LDL cholesterol levels are lower than 3.3 mmol/L (130 mg/dL). Respective goals for LDL cholesterol concentrations for high-risk patients have been recently defined by various international societies. To safely put into practice the recommendations for LDL-apheresis previously mentioned, standardized treatment guidelines for LDL-apheresis need to be established in Germany that should be supervised by an appropriate registry.     

The Lipoprotein and Coronary Atherosclerosis Study (LCAS): Design,methods, and baseline data of a trial of fluvastatin in patients without severe hypercholesterolemia

Few direct clinical data are available regarding whether cholesterol-lowering therapy should be extended to patients with coronary heart disease (CHD) and normal or only slightly elevated plasma cholesterol concentrations. The one published angiographic trial designed to examine this question found no benefit. Additional prospective data will be provided by the Lipoprotein and Coronary Atherosclerosis Study (LCAS), a randomized, double-blind, placebo-controlled trial of fluvastatin therapy (20 mg twice daily) monitored by both quantitative coronary angiography (QCA) and, in a subset of patients, positron-emission tomography (PET). Eligible subjects in LCAS were men and women 35–75 years of age with low-density lipoprotein (LDL) cholesterol of 115–190 mg/dL on stable dietary therapy and with angiographic evidence by caliper measurement of at least one coronary atherosclerotic lesion causing 30–75% diameter stenosis. Among the 429 patients randomized (mean age 58.8, 81% male), mean baseline LDL cholesterol was only 145.6 mg/dL. Any patient with mean prerandomization LDL cholesterol of 160 mg/dL or higher also received open-label adjunctive cholestyramine. The primary endpoint is within-patient per-lesion change in minimum lumen diameter (MLD) as measured by QCA at baseline and 2.5-year follow-up. All evaluable lesions had MLD at least 0.8 mm less than the reference lumen diameter at either baseline or follow-up and MLD at least 25% of the reference lumen diameter at baseline. Data obtained on myocardial perfusion changes (99 patients underwent initial PET), special lipid particles, and coagulation factors may help define which patients with CHD and relatively low LDL cholesterol will benefit from lipid-lowering treatment.     

Medical management of stable coronary artery disease

All patients with stable coronary artery disease require medical therapy to prevent disease progression and recurrent cardiovascular events. Three classes of medication are essential to therapy: lipid-lowering, antihypertensive, and antiplatelet agents. Lipid-lowering therapy is necessary to decrease low-density lipoprotein cholesterol to a target level of less than 100 mg per dL, and physicians should consider a goal of less than 70 mg per dL for very high-risk patients. Statins have demonstrated clear benefits in morbidity and mortality in the secondary prevention of coronary artery disease; other medications that can be used in addition to statins to lower cholesterol include ezetimibe, fibrates, and nicotinic acid. Blood pressure therapy for patients with coronary artery disease should start with beta blockers and angiotensin-converting enzyme inhibitors. If these medications are not tolerated, calcium channel blockers or angiotensin receptor blockers are acceptable alternatives. Aspirin is the first-line antiplatelet agent except in patients who have recently had a myocardial infarction or undergone stent placement, in which case clopidogrel is recommended. Anginal symptoms of coronary artery disease can be treated with beta blockers, calcium channel blockers, nitrates, or any combination of these. Familiarity with these medications and with the evidence supporting their use is essential to reducing morbidity and mortality in patients with coronary artery disease.     

Low-density lipoprotein apheresis for the treatment of refractory hyperlipidemia

The advent of treatment with 3-hydroxy-3-methylglutaryl coenzyme A inhibitors has meant that, with a combination of diet and drug therapy, adequate control of serum cholesterol concentrations can be achieved in most patients with hypercholesterolemia. However, some patients, primarily those with familial hypercholesterolemia (FH), may require additional therapy to lower their cholesterol levels. In recent years, low-density lipoprotein (LDL) apheresis has emerged as an effective method of treatment in these patients. The criteria for commencement of LDL apheresis are LDL cholesterol levels of 500 mg/dL or higher for homozygous FH patients, 300 mg/dL or higher for heterozygous FH patients in whom medical therapy has failed, and 200 mg/dL or higher for heterozygous FH patients with documented coronary disease and in whom medical therapy has failed. In addition to cholesterol lowering in patients with FH, other indications for LDL apheresis are emerging. These include its use in the treatment of graft vascular disease in patients receiving cardiac transplants as well as in the treatment of certain glomerulonephritides. This review examines the role of LDL apheresis in the management of lipid disorders and the evidence available to support its use in clinical practice.     

Update on managing hypercholesterolemia. The new NCEP guidelines.

1. The Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (ATPIII) will significantly increase the number of Americans treated for hypercholesterolemia. 2. The ATPIII focuses on lowering low density lipoprotein cholesterol as a primary initiative and using exercise, diet, and pharmacotherapy as a means for lowering coronary heart disease and risks. 3. The new guidelines list low density lipoprotein cholesterol levels of less than 100 mg/dL as optimal for all clients. 4. The ATPIII places increased attention on high triglyceride levels (> 200 mg/dL) and on early detection and appropriate aggressive treatment for clients at risk for coronary heart disease and events.     

Resolving hyperlipidemia after liver transplantation in a patient with primary sclerosing cholangitis

A 64-year-old man with primary sclerosing cholangitis (PSC) and resultant liver failure presented to our hospital with severe dyslipidemia (total cholesterol, 525 mg/dL; low-density lipoprotein (LDL) cholesterol, 489 mg/dL; high-density lipoprotein (HDL) cholesterol, 13 mg/dL; triglycerides, 114 mg/d) and coronary artery disease. The abnormal lipid profile of patients with cholestatic liver disease, such as PSC, includes an abnormal atherogenic LDL called lipoproteinX. The patient's dyslipidemia persisted despite treatment with a statin. Lipids normalized only after liver transplantation (total cholesterol, 135 mg/dL; LDL cholesterol, 60 mg/dL; high-density lipoprotein cholesterol, 48 mg/dL; triglycerides, 130 mg/dL). To the best of our knowledge, the dramatic improvement in the lipid profile after liver transplantation represents the first such published report for PSC. The recognition of dyslipidemia and atherosclerosis in those with cholestatic liver disease and the normalization of lipid profile after liver transplantation warrant further study. We present a review of dyslipidemia in cholestatic liver disease, its relationship to atherosclerosis, and its treatment.     

Cardiovascular medicine update 2007: perioperative risk, carotid angioplasty, drug-eluting stents, stronger statins

Some recent clinical trials have concluded the following: Patients who need noncardiac surgery and who are at risk of major cardiac events should not undergo revascularization with the aim of achieving a better perioperative outcome. They should have an office evaluation only and be prescribed a beta-blocker, if indicated. Except for unusual, high-risk cases, patients at risk of stroke due to atherosclerotic carotid artery stenosis should undergo carotid endarterectomy rather than carotid stenting. Because the technology is still developing, however, carotid stenting may still be appropriate as part of a clinical trial. Although drug-eluting coronary stents reduce the risk of restenosis in the short-term, they pose a small but significant risk of in-stent thrombosis. Clopidogrel (Plavix) should be prescribed for at least a year following drug-eluting stent placement, and perhaps indefinitely. Patients with known coronary heart disease have better outcomes if they receive aggressive statin therapy (eg, atorvastatin [Lipitor] 80 mg/day) to lower their serum levels of low-density lipoprotein cholesterol to less than 70 mg/dL.     

Lipid-lowering therapy in patients with peripheral arterial disease: are guidelines being met?

OBJECTIVES: To determine the proportion of patients with lower extremity peripheral arterial disease (PAD) who reach recommended low-density lipoprotein cholesterol (LDL-C) levels (<100 mg/dL) and to identify the patient characteristics that are independently associated with attaining the LDL-C goal (<100 mg/dL). PATIENTS AND METHODS: Eligible patients were identified from a roster of patients who had undergone testing at a nonvascular laboratory between September 1, 2001, and January 31, 2002, and were found to have evidence of PAD, defined as an ankle-brachial index of 0.9 or less. We thoroughly reviewed patients' electronic medical records. Backward elimination multivariate logistic regression modeling was used to Identify factors associated with reaching the goal LDL-C level. RESULTS: Among 143 patients with PAD, 105 (73%) met the goal LDL-C level. Lipid-lowering therapy was prescribed for 109 (76%). Lower diastolic blood pressure and lower weight were independently associated with an LDL-C level of less than 100 mg/dL. CONCLUSION: We found higher rates of lipid-lowering therapy in patients with PAD than reported previously. Patients with diabetes mellitus or coronary artery disease were not more likely to meet the goal LDL-C level than those without these comorbidities. Clinical practice may be catching up to clinical guidelines.     

Management of hypertriglyceridemia

Hypertriglyceridemia is associated with an increased risk of cardiovascular events and acute pancreatitis. Along with lowering low-density lipoprotein cholesterol levels and raising high-density lipoprotein cholesterol levels, lowering triglyceride levels in high-risk patients (e.g., those with cardiovascular disease or diabetes) has been associated with decreased cardiovascular morbidity and mortality. Although the management of mixed dyslipidemia is controversial, treatment should focus primarily on lowering low-density lipoprotein cholesterol levels. Secondary goals should include lowering non-high-density lipoprotein cholesterol levels (calculated by subtracting high-density lipoprotein cholesterol from total cholesterol). If serum triglyceride levels are high, lowering these levels can be effective at reaching non-high-density lipoprotein cholesterol goals. Initially, patients with hypertriglyceridemia should be counseled about therapeutic lifestyle changes (e.g., healthy diet, regular exercise, tobacco-use cessation). Patients also should be screened for metabolic syndrome and other acquired or secondary causes. Patients with borderline-high serum triglyceride levels (i.e., 150 to 199 mg per dL [1.70 to 2.25 mmol per L]) and high serum triglyceride levels (i.e., 200 to 499 mg per dL [2.26 to 5.64 mmol per L]) require an overall cardiac risk assessment. Treatment of very high triglyceride levels (i.e., 500 mg per dL [5.65 mmol per L] or higher) is aimed at reducing the risk of acute pancreatitis. Statins, fibrates, niacin, and fish oil (alone or in various combinations) are effective when pharmacotherapy is indicated.     

Circulating electronegatively charged low-density lipoprotein in patients with angiographically documented coronary artery disease

There is growing experimental evidence to suggest the role of oxidatively modified low-density lipoprotein (LDL) in the initiation and progression of atherosclerosis. The oxidation of lipoprotein moiety causes modification of positively charged lysine residues and results in negative net charge of lipoprotein particles. OBJECTIVE: To measure the amount of circulating electronegatively charged LDL particles (LDL-) in plasma of patients with angiographically documented coronary artery disease (CAD). METHODS: Thirty patients were assigned to the study group (CAD+) and 10 patients to the control group (Ctrl). LDL- was quantitated in homogeneous LDL fractions obtained by ultracentrifugation, using ion exchange high performance liquid chromatography. Plasma lipids were measured using enzymatic kits. RESULTS: The CAD+ group had significantly higher levels of LDL- in the whole LDL fraction (7.66+/-1.92 vs. 5.14+/-0.84%, p=0.0003). Moreover the CAD+ group had significantly higher levels of total cholesterol (255.4+/-35.1 vs. 210.4+/-22.4 mg/dL), LDL cholesterol (154.5+/-26.9 vs. 122.4+/-21.1 mg/dL) and significantly lower levels of high-density lipoprotein (HDL) cholesterol (40.4+/-9.4 vs. 51.0+/-11.5 mg/dL). LDL- remained significantly higher in the CAD+ group after adjustment for total cholesterol, LDL cholesterol and HDL cholesterol (6.3 vs. 5.14% at p=0.0095). There is a trend towards a positive correlation between LDL- levels and LDL cholesterol in the control group (Spearman R=0.55 at p=0.098). CONCLUSIONS: Electronegatively charged LDL appears to be an additional hallmark of coronary artery disease, independently of established lipid risk factors. The trend towards a positive correlation between LDL cholesterol concentration and the level of LDL- in the control group may reflect the susceptibility of LDL cholesterol to autoxidation, Moreover, this may indicate other oxidative mechanisms in coronary artery disease. Nonetheless, further studies assessing the prognostic value of electronegatively charged LDLs are necessary.     

Effective use of statins to prevent coronary heart disease

Primary and secondary prevention trials have shown that use of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (also known as statins) to lower an elevated low-density lipoprotein cholesterol level can substantially reduce coronary events and death from coronary heart disease. In 1987 and 1993, the National Cholesterol Education Program promulgated guidelines for cholesterol screening and treatment. Thus far, however, primary care physicians have inadequately adopted these guidelines in clinical practice. A 1991 study found that cholesterol screening was performed in only 23 percent of patients. Consequently, many patients with elevated low-density lipoprotein levels and a high risk of primary or recurrent ischemic events remain unidentified and untreated. A study published in 1998 found that fewer than 15 percent of patients with known coronary heart disease have low-density lipoprotein levels at the recommended level of below 100 mg per dL (2.60 mmol per L). By identifying patients with elevated low-density lipoprotein levels and instituting appropriate lipid-lowering therapy, family physicians could help prevent cardiovascular events and death in many of their patients.     

Low-density lipoprotein apheresis using the liposorber dextran sulfate cellulose system for patients with hypercholesterolemia refractory to medical therapy

A subset of patients with familial hypercholesterolemia (FH) have an inadequate lipid-lowering response to diet and drug treatment and should be considered for low-density lipoprotein (LDL)-apheresis therapy. This procedure selectively removes apolipoprotein B-containing particles [LDL, very-low-density lipoprotein, lipoprotein(a)] from plasma independent of diet and drug therapy. Methods for performing LDL-apheresis include dextran sulfate cellulose adsorption, immunoadsorption, and heparin-induced extracorporeal precipitation. The Liposorber Study Group evaluated LDL removal using the Liposorber® LA-15 LDL-apheresis System in 64 patients with FH who had not responded adequately to diet and maximal drug therapy. Mean acute reductions in LDL cholesterol (LDL-C) were 76% in heterozygous FH (HtFH) patients and 81% in homozygous FH (HoFH) patients. Time-averaged levels of LDL-C were lowered 41% in HtFH and 53% in HoFH patients. Hypotension was the most frequent side effect, occurring in 3% of procedures. The Liposorber® LA-15 System has been approved by the Food and Drug Administration and is recommended for 1) patients with functional homozygous FH (LDL-C level >500 mg/dL; 2) patients with coronary artery disease (CAD) and LDL-C levels ≥200 mg/dL; 3) patients without CAD, but an LDL-C level ≥300 mg/dL. © 1996 Wiley-Liss, Inc.     

Relation between lipoprotein (a) and in vitro oxidation of apolipoprotein B-containing lipoproteins

OBJECTIVES: To assess the relationship between lipoprotein (a) [Lp (a)] and lipoprotein oxidation in patients with coronary artery disease (CAD). DESIGN AND METHODS: Oxidation of apolipoprotein (apo)B-containing lipoproteins, vitamin E, carotenoids, lipid-lipoprotein levels were determined in 171 CAD and 70 non-CAD subjects. RESULTS: In CAD patients with Lp (a) concentrations >/= 30 mg/dL; total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), malondialdehyde (MDA), and apo B levels were significantly higher and lag-time and age were significantly lower than those of CAD patients with Lp (a) concentrations < 30 mg/dL. In non-CAD subjects with Lp (a) concentrations >/= 30 mg/dL; TC, LDL-C, and vitamin E levels were significantly higher and lag-time was significantly lower than those of non-CAD subjects with Lp (a) concentrations < 30 mg/dL. In CAD patients, Lp (a) correlated negatively with lag-time and positively with MDA levels. Lp (a) correlated negatively with lag-time and vitamin E levels in non-CAD subjects. CONCLUSIONS: We have shown that plasma apo B-containing lipoproteins of both CAD and non-CAD subjects with Lp (a) levels >/= 30 mg/dL are more susceptible to in vitro oxidative modification than those of subjects with Lp (a) levels < 30 mg/dL. The relationship between Lp (a) and enhanced susceptibility of apo B-containing lipoproteins to oxidation, appears to support routine investigation of Lp (a).     

Clinical diagnosis of lipid disorders

Atherosclerotic cardiovascular disease is a major health problem in the United States. In particular, coronary heart disease (CHD) is the leading cause of death in men and women in the United States, as well as in other industrialized countries. Extensive observational epidemiologic data within and between populations have strongly linked such various factors as untreated hypertension, diabetes, cigarette smoking, and lipid abnormalities to the development of CHD. With respect to lipoprotein parameters, elevated total and low-density lipoprotein cholesterol (LDL-C) and low levels of high-density lipoprotein cholesterol (HDL-C) have been strongly associated with CHD risk. Emerging evidence suggests that other lipoprotein abnormalities also are associated with premature CHD, including elevated levels of lipoprotein(a), triglyceride-rich lipoproteins such as small very-low-density lipoproteins and intermediate-density lipoproteins, small and dense LDL particles, and the magnitude of postprandial lipemia. Extensive primary and secondary clinical trial evidence has established that favorably altering dyslipidemias through diet and a variety of pharmacologic agents produces clear improvements in CHD end points. The extent of this benefit depends on the presence or absence of clinical atherosclerotic disease, as well as other CHD risk factors, and the severity of one or more lipoprotein abnormalities. CHD patients and individuals with multiple risk factors, but free of clinical CHD, derive the greatest absolute benefit from lipid treatment directed at reducing LDL-C. The dyslipidemias that impart high risk are severely elevated LDL-C (> 200 mg/dL), combined high LDL-C and low HDL-C (< 35 mg/dL), and combined hyperlipidemias (non-HDL-C > 200 mg/dL with low HDL). The purpose of this review is to aid the primary care physician in identifying these important dyslipidemias and to critically analyze the relative importance of various lipoproteins on atherosclerotic risk.     

Coronary atherosclerosis can regress with very intensive statin therapy

The ASTEROID trial (JAMA 2006; 295:1556-1565) showed that very intensive statin therapy with rosuvastatin 40 mg once daily results in highly significant regression of coronary atherosclerosis as assessed by serial intravascular ultrasonography (IVUS). The mean low-density lipoprotein cholesterol (LDL-C) level achieved with this regimen was 61 mg/dL, and the mean high-density lipoprotein cholesterol (HDL-C) level increased by 15%. While the merits of concomitant LDL-C-lowering and HDL-C-raising therapies remain to be determined, the results of the ASTEROID and other recent trials suggest that the optimal strategy for lipid-lowering in patients with coronary artery disease is to try for the lowest LDL-C level that can be attained without adverse effects.     

Hypercholesterolemia in diabetes and glucose intolerance in the U.S. population

The prevalence of hypercholesterolemia, according to the guidelines of the National Cholesterol Education Program, has been determined in a national survey of diabetes and glucose intolerance. Rates of elevated total cholesterol in people with diabetes in the United States are only slightly greater than in those without diabetes after adjusting for age and sex. Nevertheless, high or borderline high total cholesterol is common in diabetes and is present in 70% of adults with diagnosed diabetes and 77% with undiagnosed diabetes in the U.S. population. Of these individuals, 95% have evidence of coronary heart disease or two or more risk factors for heart disease and should therefore have their low-density lipoprotein (LDL) cholesterol measured. Based on our national data, LDL cholesterol levels warranting dietary treatment for hypercholesterolemia would be expected in 85% of these people. Although elevated LDL cholesterol is uncommon in people with diabetes who have total cholesterol of less than 200 mg/dl, other risk factors for coronary heart disease are very frequent (100% of men, 73% of women), and low total and LDL cholesterol may mask low high-density lipoprotein cholesterol. Therefore, investigation of blood lipid levels and coronary heart disease risk factors should be routine in all patients with diabetes, and treatment strategies should include management of lipid disorders and the multiple other risk factors for coronary heart disease that are highly prevalent in these patients.     

Assessment of compliance with lipid guidelines in an academic medical center

BACKGROUND: The importance of achieving a low-density lipoprotein cholesterol (LDL-C) level less than 100 mg/dL in patients with coronary artery disease (CAD) or cerebrovascular disease (CVD) is well established. Emerging evidence supports the recognition and management of secondary lipid goals, high-density lipoprotein cholesterol (HDL-C) level greater than 40 mg/dL, and triglyceride level less than 150 mg/dL. OBJECTIVE: To evaluate whether inpatient services within an academic setting were achieving/addressing primary and secondary lipid goals in patients with established CAD or CVD. METHODS: Patients with a discharge diagnosis of acute myocardial infarction, myocardial revascularization procedures, and/or ischemic stroke were identified. A retrospective chart review was done to assess adherence to the American Heart Association (AHA)/American College of Cardiology (ACC) guidelines for lipid management. RESULTS: On average, 63% of patients with CAD or CVD had a lipid panel assessed during their hospitalization. Of the patients who had a fasting lipid panel checked, only 40% (72/178) had an LDL-C level less than 100 mg/dL. Of those patients, only 31% (22) also had an HDL-C level greater than 40 mg/dL. Even fewer patients (24%; 17) met both primary and secondary goals. Of the 287 patients included in the study, 69% (199) were prescribed a statin, 3% (9) a fibrate, and 3% (8) niacin on discharge. CONCLUSIONS: Few patients with CAD or CVD met the AHA/ACC goals for lipid management, yet a significant number were not prescribed appropriate lipid-lowering therapy at discharge. This finding strongly suggests that more awareness in this area is needed.     

Meaning of low-density lipoprotein-apheresis for hypercholesterolemic patients at high risk for recurrence of coronary heart disease.

The goal of cholesterol-lowering therapy in hypercholesterolemic patients at high risk for recurrence of coronary heart disease (CHD) is the prevention of acute coronary syndrome by stabilization of coronary atheromatous plaque. We often encounter patients in whom it is difficult to maintain the serum cholesterol level at a desirable level with dietary therapy and drug treatment, despite the development and use of statins. For secondary prevention in patients who are at high risk for the recurrence of CHD and whose cholesterol level cannot be controlled by drugs alone, low-density lipoprotein (LDL)-apheresis therapy, which involves removal of LDL through extracorporeal circulation, is now available. Many reports concerning improvement of vascular endothelial function, improvement of myocardial ischemia, regression of coronary atherosclerotic lesions, stabilization of coronary plaque, and reduction in the incidence of cardiac events as a result of LDL-apheresis treatment have been published in various countries. We believe that LDL-apheresis should be performed on hypercholesterolemic patients with existing CHD for whom diet and maximum cholesterol-lowering drug therapies have been ineffective or not tolerated and whose LDL cholesterol level is 160 mg/dL or higher.     

Prognostic evaluation of primary non-small cell lung carcinoma patients using biological fluid variables. A systematic review

There is growing experimental evidence to suggest the role of oxidatively modified low‐density lipoprotein (LDL) in the initiation and progression of atherosclerosis. The oxidation of lipoprotein moiety causes modification of positively charged lysine residues and results in negative net charge of lipoprotein particles. Objective: To measure the amount of circulating electronegatively charged LDL particles (LDL–) in plasma of patients with angiographically documented coronary artery disease (CAD). Methods: Thirty patients were assigned to the study group (CAD+) and 10 patients to the control group (Ctrl). LDL– was quantitated in homogeneous LDL fractions obtained by ultracentrifugation, using ion exchange high performance liquid chromatography. Plasma lipids were measured using enzymatic kits. Results: The CAD+ group had significantly higher levels of LDL– in the whole LDL fraction (7.66±1.92 vs. 5.14±0.84%, p=0.0003). Moreover the CAD+ group had significantly higher levels of total cholesterol (255.4±35.1 vs. 210.4±22.4?mg/dL), LDL cholesterol (154.5±26.9 vs. 122.4±21.1?mg/dL) and significantly lower levels of high‐density lipoprotein (HDL) cholesterol (40.4±9.4 vs. 51.0±11.5?mg/dL). LDL– remained significantly higher in the CAD+ group after adjustment for total cholesterol, LDL cholesterol and HDL cholesterol (6.3 vs. 5.14% at p=0.0095). There is a trend towards a positive correlation between LDL– levels and LDL cholesterol in the control group (Spearman R=0.55 at p=0.098). Conclusions: Electronegatively charged LDL appears to be an additional hallmark of coronary artery disease, independently of established lipid risk factors. The trend towards a positive correlation between LDL cholesterol concentration and the level of LDL– in the control group may reflect the susceptibility of LDL cholesterol to autoxidation, Moreover, this may indicate other oxidative mechanisms in coronary artery disease. Nonetheless, further studies assessing the prognostic value of electronegatively charged LDLs are necessary.