Lack of concordance in classification of coronary heart disease risk: high-risk HDL cholesterol less than 35 mg/dl in subjects with desirable total serum cholesterol, less than 200 mg/dl

In using National Cholesterol Education Program guidelines (for desirable low risk, a total cholesterol level less than 200 mg/dl, and for high risk, a level of high-density lipoprotein cholesterol (HDLC) less than 35 mg/dl), our specific aim was to examine lack of concordance in classification of coronary heart disease (CHD) risk by HDLC less than 35 mg/dl in subjects with total cholesterol less than 200 and to determine whether lack of concordance increased as group CHD risk increased. We studied four cohorts ranging from putatively low to high CHD risk. These included self-referred subjects in a public urban total cholesterol screening (n = 897), hospitalized patients with depression (n = 144), Cholesterol Center referrals at presumed high CHD risk (n = 1120), and patients having coronary arteriography (n = 145) because of presumed coronary artery disease. Total cholesterol was less than 200 mg/dl in 25% of subjects from the urban sampling, in 54% of hospitalized patients with depression, in 27% of Cholesterol Center referrals, and in 41% of those undergoing cardiac catheterization. In these four cohorts, of subjects with total cholesterol less than 200, 7%, 26%, 25%, and 48%, respectively, had HDLC less than 35 mg/dl. The likelihood of having total cholesterol less than 200 and HDLC less than 35 mg/dl was 1.7% in urban public subjects, 6.8% in Cholesterol Center referrals, 13.9% in depressed patients, and 20% in cardiac catheterization patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

Low-dose, time-release nicotinic acid: effects in selected patients with low concentrations of high-density lipoprotein cholesterol.

In a retrospective analysis, 63 participants in a cardiac rehabilitation-preventive cardiology program were identified as having low blood concentrations (mean, 34 mg/dl) of high-density lipoprotein cholesterol (HDL-C) and a mean total cholesterol level of 223 mg/dl after 3 months of hygienic measures (aerobic exercise, avoidance of tobacco, diet, and weight loss) designed to increase the HDL-C level. These patients (treatment group) were treated with low-dose, time-release nicotinic acid (mean, 1,297 mg/day) for a mean duration of 7.4 months. All subjects were able to take the drug without intolerable side effects. Fifty-four patients similar to those in the treatment group participated in the same program but were not treated with nicotinic acid (control group). Exercise, diet, body weight, and smoking remained stable throughout the period of observation. For the treatment group, HDL-C levels increased a mean of 18% (+6 mg/dl), total cholesterol concentrations decreased 9% (-20 mg/dl), the ratio of total cholesterol to HDL-C decreased 25% (from 6.8 to 5.1), low-density lipoprotein cholesterol levels decreased 13% (-20 mg/dl), and triglyceride levels decreased 20% (from 165 mg/dl to 132 mg/dl). Aspartate aminotransferase and uric acid concentrations were minimally increased after treatment, and the blood glucose level was unchanged. In the control group, HDL-C levels increased a mean of 8% (+3 mg/dl) and the other blood lipid variables were not improved after a mean of 8.3 additional months of diet and exercise.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cholesterol guidelines, lipoprotein cholesterol levels, and triglyceride levels: potential for misclassification of coronary heart disease risk

By using National Cholesterol Education Program guidelines for serum cholesterol (less than 200 mg/dl is designated "desirable," and 200 to 239 mg/dl is designated "borderline-high," and greater than or equal to 240 mg/dl is designated "high"), low-density and high-density lipoprotein (LDL, HDL) cholesterol levels and triglyceride levels were quantitated in 897 self-referred fasting subjects to assess the potential for coronary risk misclassification. With cholesterol less than 200 mg/dl, misclassification was arbitrarily identified by an LDL level greater than or equal to the 75th percentile, a triglyceride level greater than or equal to the 90th percentile, or an HDL level less than or equal to the 10th percentile. With the cholesterol level in the 200 to 239 mg/dl range, misclassification was identified by an LDL level greater than or equal to the 75th percentile, a triglyceride level greater than or equal to the 90th percentile, and an HDL level less than or equal to the 10th percentile or greater than or equal to the 90th percentile (or both). With a cholesterol level greater than or equal to 240 mg/dl, misclassification was identified by an HDL level less than or equal to the 10th percentile, or greater than or equal to the 90th percentile. With the cholesterol level less than 200 mg/dl, misclassification is rare, occurring in 14.5% of the subjects. With the cholesterol level in the 200 to 239 mg/dl range, and greater than or equal to 240 mg/dl, misclassification occurred in 46.7% and 17.6% of the subjects, respectively. The importance of routine lipoprotein analysis when the cholesterol level is greater than or equal to 240 mg/dl is emphasized by the finding that 65% of the subjects in this category had top quartile LDL levels, 8% had bottom decile HDL levels, and 30% had top decile triglyceride levels. To avoid misclassification, fasting HDL, LDL, and triglyceride levels should probably be measured in all subjects with screening cholesterol levels greater than or equal to 200. There is remarkably little misclassification with top quartile LDL or bottom decile HDL levels (or both) when the cholesterol level is less than 200 mg/dl.     

Simvastatin in the treatment of hypercholesterolemia in elderly patients

Twenty elderly (mean age, 69 years), hypercholesterolemic patients (low-density lipoprotein [LDL] levels greater than or equal to 160 mg/dl) were supplied a lipid-lowering diet for one month and then received 10 mg of simvastatin daily for 12 months. Total cholesterol levels fell significantly, from 304.6 mg/dl at baseline to 277.4 mg/dl after one month on the diet, to 245.9 mg/dl after one month of simvastatin, and to 216.1 mg/dl after two months of simvastatin; total cholesterol levels remained significantly lower (221.6 mg/dl at month 12). LDL levels decreased significantly, from 217.6 mg/dl at baseline to 130.4 mg/dl at month 12. High-density lipoprotein levels increased significantly only at months 2 and 3. Apolipoprotein (apo) A levels increased significantly, from 147.2 mg/dl at baseline to 217.9 mg/dl at month 12. There were no significant changes in triglyceride or apo B levels. No changes in blood pressure, heart rate, or body weight or in results of laboratory tests were noted. Few side effects were reported. It is concluded that simvastatin is safe and effective in the treatment of hypercholesterolemia in elderly patients.     

Plasma exchange in severe hypertriglyceridemia a clinical study.

BACKGROUND: Hypercholesterolemia and hypertriglyceridemia are independent risk factors for atherosclerotic heart diseases. Moreover acute pancreatitis may occur in patients with severe hypertriglyceridemia. AIM OF THE STUDY: To evaluate the effectiveness of plasma exchange (PE) in patients with severe hypertriglyceridemia. METHODS: Seven patients with severe hypertriglyceridemia (a triglyceride level of more than 1000mg/dl) were treated with PE. After PE, lipid and hematological parameters and side effects were evaluated. RESULTS: Triglyceride levels decreased below 1000mg/dl in all patients. The levels of triglyceride and very low-density lipoprotein cholesterol (p<0.05 for both), and total cholesterol (p<0.005) decreased significantly. PE was well-tolerated. Liver and renal functions, hematological parameters, except for an increase in white blood cell counts, did not change significantly. CONCLUSION: PE may be used safely and effectively in severe hyperlipidemic patients at risk of acute coronary events and acute pancreatitis. Further extended studies may provide more detailed information.     

Efficacy and tolerability of lovastatin in elderly hypercholesterolemic patients.

In a previously published multicenter study (Kannel and associates, 1990), the effects of six months' treatment with lovastatin were evaluated in patients with hypercholesterolemia. In the present report the results from the 144 elderly patients (aged 65 to 83 years) are presented and compared with those from the 343 patients aged less than 65 years. The initial dose of lovastatin was 20 mg daily and could be increased to a maximum of 80 mg/day. After one month of treatment, in both the elderly and younger patients, levels of total cholesterol, low-density lipoprotein (LDL) cholesterol, very-low-density lipoprotein cholesterol, and triglycerides, and the total cholesterol: high-density lipoprotein (HDL) cholesterol and LDL:HDL [corrected] cholesterol ratios were significantly lower and high-density lipoprotein cholesterol levels were significantly higher. These improvements in the lipid profile were maintained for six months in both patient groups. LDL cholesterol goals of less than 130 mg/dl in patients with coronary heart disease (CHD) or two CHD risk factors and less than 160 mg/dl among the other patients were achieved by 53% of the elderly patients and 40% of the younger patients at one month (P less than 0.01) and by 62% and 47% at six months (P less than 0.01). By the end of the study, the mean daily dose of lovastatin was 35.4 mg for the elderly and 38.4 mg for the younger patients. The drug was generally well tolerated by all patients. The results indicate that both elderly and younger hypercholesterolemic patients respond well to treatment with lovastatin.     

Prevalence of hypercholesterolaemia and coronary heart disease risk factors among Southeast Asian refugees in a primary care clinic

The National Cholesterol Education Program's guidelines for the detection, evaluation, and treatment of high serum cholesterol in adults were employed in screening 155 Southeast Asian refugees in a primary care clinic in Seattle, Washington. In order to determine the need for a therapeutic intervention, information also was collected on the presence of other coronary heart disease (CHD) risk factors. Male gender (39%), cigarette smoking (27%) and hypertension (26%) were the most common CHD risk factors; diabetes mellitus, obesity, a family or prior history of CHD or cerebral/peripheral vascular disease were each noted in less than 10%. The mean serum total cholesterol was 194 mg/dl. Thirty–seven (24%) patients required further lipoprotein analysis based on cholesterol level, history of CHD and risk factors for CHD. Twenty–one (66%) of 32 patients who underwent lipoprotein analysis (14% of all patients) were candidates for a therapeutic intervention for hypercholesterolaemia. Additionally, 14 (44%) patients undergoing lipoprotein analysis had depressed high–density lipoprotein levels (< 35 mg/dl). We conclude that CHD risk factors including hypercholesterolaemia are common in Southeast Asian refugee clinic patients and that in many, a therapeutic intervention may well be justified. Southeast Asian refugees should be routinely screened for hypercholesterolaemia and other CHD risk factors in accordance with the National Cholesterol Education Program's guidelines.     

High density lipoprotein cholesterol concentrations in physically active and sedentary spinal cord injured patients

Individuals with traumatic spinal cord injury (SCI) are extremely inactive yet little is known about the long-term consequences of chronic inactivity. Current research investigated the concentrations of high density lipoprotein cholesterol (HDLc) and its subfractions HDL2 and HDL3 in 66 extremely sedentary SCI admissions to a rehabilitation center. High density lipoprotein cholesterol is a primary risk factor for cardiovascular disease with decreased levels associated with increased cardiovascular risk. The concentrations of HDLc observed in the SCI sedentary population were compared with 22 olympic caliber wheelchair athletes (SCI athletes) and 126 able-bodied controls. Total HDLc, HDL2, and HDL3 was significantly lower in the male SCI sedentary population (34.2 mg/dl, 8.9 mg/dl, 25.3 mg/dl) than the male SCI athletes (42.7 mg/dl, 13.9 mg/dl, 28.8 mg/dl) or male able-bodied control populations (47.1mg/dl, 11.3mg/dl, 35.8 mg/dl). A similar pattern emerged for the female subjects. The reduction in HDLc seen in the SCI sedentary would predict over a 60% increased risk of heart attack compared to nondisabled controls. The primary difference between the two SCI groups was the level of physical activity, suggesting that this may be an important parameter for elevating total HDLc and HDL2, and presumably decreasing the risk for coronary heart disease. Therefore, physical activity positively affects total HDL and the supposedly antiatherogenic subfraction HDL2 in the SCI patient.     

Xanthelasma: clinical indicator of decreased levels of high-density lipoprotein cholesterol

The fasting plasma lipid and lipoprotein levels were measured prospectively in 41 consecutive patients with xanthelasma seen over a four-year period. The study group included 25 women and 16 men with mean ages of 60 and 56 years, respectively. Each patient had clinical evaluation for medications or illnesses that might affect plasma lipid levels before entry into the study. The most striking lipid abnormality was the preponderance of decreased levels of high-density lipoprotein cholesterol (HDL-C). In 94% of the study population, HDL-C values were less than the mean values of the age-matched reference population. For men the mean HDL-C level was 30.8 mg/dl (vs 45 mg/dl in the reference population, P less than .001); for women the mean HDL-C level was 33 mg/dl (vs 50 mg/dl, P less than .001). The total cholesterol, low-density lipoprotein, and triglyceride levels of those in the study were not significantly different from those of the patients in the reference population. Evaluation of cardiac risk based solely on HDL-C levels showed 80% of the study population to have three to four times the average risk. This study points out the high probability of decreased HDL-C levels in patients with xanthelasma. Since the level of HDL-C has been shown to be inversely related to the incidence of cardiovascular disease, it may be prudent to evaluate HDL-C levels and do a thorough cardiovascular evaluation in patients with xanthelasma.     

Estimation of cardiovascular risk: total cholesterol versus lipoprotein profile

Summary The complete lipoprotein profile is thought to give more information about the individual risk of coronary heart disease than total cholesterol alone. Although total cholesterol has a low sensitivity in the correct assessment of the risk of coronary heart disease, it may be of value in screening programs because of its low cost. In this study of 5,335 subjects, total cholesterol gave a different assessment of coronary heart disease risk (United States National Cholesterol Education Program guidelines) in 25% of subjects than the complete lipoprotein profile. Differences in risk assignment were mainly accounted for by high- and low-density lipoprotein-cholesterol (Friedewald equation). The calculated low-density lipoprotein-cholesterol was highly correlated with the value measured with a mixed ultracentrifugation and precipitation procedure. However, calculated values gave estimates of coronary heart disease risk which were 20% different from those from measure values. In 200 subjects in whom the lipoprotein profile was assessed three times in 1 year, the total cholesterol low-density lipoprotein-cholesterol varied by more than 30 mg/dl (0.78 mmol/l) in 52% and 50%, respectively, triglycerides by more than 30 mg/dl (0.34 mmol/l) in 75%, and high-density lipoprotein-cholesterol by more than 15 mg/dl (0.39 mmol/l) in 34%. Compared with the mean of the measurements, the single measurement of total cholesterol misclassified 48% of subjects, low-density lipoprotein-cholesterol 60%, high-density lipoprotein-cholesterol 12%, and 28%. We conclude that total cholesterol alone may be misleading in the assignment of coronary heart disease risk. Calculation of low-density lipoprotein-cholesterol, although less accurate than desirable, is the only way of evaluating this in clinical practice. Finally, repeated lipid measurements are required to assess coronary heart disease risk accurately.     

Liver-directed gene transfer and prolonged expression of three major human ApoE isoforms in ApoE-deficient mice.

Apolipoprotein E (apoE) plays a key role in lipoprotein metabolism and may have other important biological functions. In humans, there are three common, naturally occurring isoforms of apoE that are associated with differences in lipid levels and atherosclerosis. However, the direct in vivo effects of the apoE isoforms on lipoprotein metabolism and atherosclerosis are not yet fully understood. To investigate the effect of the apoE isoforms in vivo, we constructed second-generation recombinant adenoviruses encoding each of the apoE isoforms. These recombinant adenoviruses were injected intravenously into apoE-deficient mice fed a Western diet (mean baseline cholesterol level 1401 mg/dl) in order to study their effects in the absence of endogenous mouse apoE. Hepatic expression of apoE3 and apoE4 completely normalized the lipoprotein profile; 3 d after injection, mean plasma cholesterol levels were 194 and 217 mg/ dl, respectively, and this effect was maintained for at least 6 wk. Expression of apoE2 had much less effect on lipoprotein levels (mean cholesterol level 752 mg/dl 3 d after injection), despite much higher plasma levels of apoE2 compared with apoE3 and apoE4; by 6 wk after injection the cholesterol levels had returned to baseline levels in the apoE2-expressing mice. Expression of all three isoforms significantly increased HDL cholesterol levels by approximately threefold and was independent of the cholesterol-lowering effect. ApoE transgene expression was substantially prolonged compared with that achieved using a first generation adenovirus and apoE was readily detected in plasma 3 mo after virus injection. These studies demonstrate: (a) prolonged in vivo expression of human apoE isoforms in apoE deficient mice after second-generation recombinant adenovirus-mediated somatic gene transfer; and (b) significantly impaired ability of apoE2 in vivo to mediate clearance of remnant lipoproteins in apoE-deficient mice fed a Western diet compared with apoE3 and apoE4.     

Effects of gamma-oryzanol on serum lipids and apolipoproteins in dyslipidemic schizophrenics receiving major tranquilizers

The subjects were 20 chronic schizophrenic patients with dyslipidemia (total cholesterol levels greater than or equal to 220 mg/dl, triglycerides greater than or equal to 150 mg/dl, or high-density lipoprotein cholesterol less than or equal to 40 mg/dl) who had been receiving neuroleptics for a mean of ten years. Each patient was given 100 mg of gamma-oryzanol three times daily for 16 weeks. Total cholesterol and low-density lipoprotein cholesterol levels, respectively, decreased significantly, from 204 and 124 mg/dl at baseline to 176 and 101 mg/dl at week 12. High-density lipoprotein cholesterol levels were 36.1 mg/dl at baseline and 35.9 mg/dl at week 12. Apolipoprotein (apo) B levels decreased significantly from 116 mg/dl to 101 mg/dl at week 16; apo A-II levels increased significantly from 31.7 mg/dl to 34.7 mg/dl; and the apo B/apo A-I ratio declined significantly from 0.99 to 0.84. No treatment side effects were recorded. It is concluded that gamma-oryzanol is safe and effective in the treatment of dyslipidemia.     

Diet and coronary heart disease. Helping patients reduce serum cholesterol level

Although coronary heart disease (CHD) remains the No. 1 cause of death in the United States, the CHD mortality rate has shown a recent decline. This has been attributed to lower fat consumption in the general population, with associated lower serum cholesterol levels. Thus, diet seems to be an important factor in controlling cholesterol level. Acting on this hypothesis, primary care physicians can help patients make appropriate dietary changes. We believe that persons at risk of hypercholesterolemia need to be identified in adolescence by measurement of total serum cholesterol level and that testing should be done every two years after age 25. The American Heart Association's prudent diet is recommended for all patients, especially those with a serum cholesterol level above 240 mg/dl. When dietary restriction does not bring the level within this limit, use of cholesterol-lowering agents is considered. To be lasting, dietary change must be gradual; realistic immediate and long-term goals should be established. In addition, the diet must be nutritionally sound and the patient must receive support from family members.     

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.     

Preventing, stopping, or reversing coronary artery disease--triglyceride-rich lipoproteins and associated lipoprotein and metabolic abnormalities: the need for recognition and treatment

A substantial number of treated patients with or at high risk for coronary artery disease continue to have fatal and nonfatal coronary artery events in spite of significant reduction of elevated levels of low-density lipoprotein cholesterol. Other lipoprotein abnormalities besides an elevated level of low-density lipoprotein cholesterol contribute to risk of coronary artery disease and coronary artery events, and the predominant abnormalities that appear to explain much of this continued risk are an elevated serum triglyceride level and a low level of high-density lipoprotein cholesterol. Most patients with coronary artery disease have a mixed dyslipidemia with hypertriglyceridemia, which is associated and metabolically intertwined with other atherogenic risk factors, including the presence of triglyceride-rich lipoprotein remnants, low levels of high-density lipoprotein cholesterol, small, dense, low-density lipoprotein particles, postprandial hyperlipidemia, and a prothrombotic state. Aggressive treatment of these patients needs to focus on these other lipoprotein abnormalities as much as on low-density lipoprotein cholesterol. Combination drug therapy will usually be required. Reliable assessment of risk of coronary artery disease from lipoprotein measurements and response to therapy requires inclusion of all atherogenic lipoproteins in laboratory measurements and treatment protocols. At present this may be best accomplished by use of non-high-density lipoprotein cholesterol (total cholesterol minus high-density lipoprotein cholesterol) calculated from standard laboratory lipoprotein values. Ultimately, a more comprehensive assessment of coronary artery disease risk and appropriate therapy may include measurement of lipoprotein subclass distribution including determination of low-density lipoprotein particle concentration and sizes of the various lipoprotein particles.     

Effects of a new calcium channel blocker, TA 3090, on serum lipoprotein levels in mild to moderate essential hypertension

The 25 hypertensive patients received 20 to 40 mg of TA 3090 daily for 12 weeks. Blood pressures declined significantly during treatment, from a mean of 162/98 to 145/88 mmHg. There were no significant changes in levels of total or very low-density lipoprotein cholesterol or triglyceride, in levels of low-density lipoprotein cholesterol, high-density lipoprotein (HDL) cholesterol, HDL2 cholesterol, HDL3 cholesterol, or in levels of apolipoprotein (apo) B, C-II, C-III, or E. Apo A-I and A-II levels increased significantly from 130 and 29.2 mg/dl before treatment to 152 and 31.4 mg/dl at 12 weeks. Mean serum creatinine levels decreased significantly from 0.92 to 0.80 mg/dl. No other drug-related changes in laboratory test results or side effects were noted. It is concluded that TA 3090 is a safe and effective treatment for mild to moderate hypertension.     

Lipids and apolipoproteins in patients treated with major tranquilizers

The concentrations of lipids and apolipoproteins in serum from men with chronic schizophrenia who were receiving major tranquilizers (17 receiving phenothiazines and 14 receiving a butyrophenone) were quantitated and compared with serum from male controls (n = 14). Concentrations of high-density lipoprotein cholesterol and apolipoproteins A-I and A-II were significantly lower in the patients than in the controls. Mean apolipoproteins C-II and C-III and very low-density lipoprotein cholesterol levels in the patients receiving phenothiazines were higher than levels in the patients receiving butyrophenone or in the controls. There were no significant differences in levels of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, or apolipoproteins B and E. The triglyceride level in patients receiving phenothiazines (163 +/- 65 mg/dl) was higher than that in patients receiving butyrophenone (104 +/- 52 mg/dl). Our data suggest that, with respect to triglyceride metabolism, butyrophenone is more beneficial than are phenothiazines.     

Atorvastatin and micronized fenofibrate alone and in combination in type 2 diabetes with combined hyperlipidemia

OBJECTIVE: This study evaluated the effect of a atorvastatin-fenofibrate combination on lipid profile, in comparison to each drug alone, in patients with type 2 diabetes and combined hyperlipidemia (CHL). RESEARCH DESIGN AND METHODS: A total of 120 consecutive patients, who were free of coronary artery disease (CAD) at entry, were studied for a period of 24 weeks. These patients were randomly assigned to atorvastatin (20 mg/day, n = 40), micronized fenofibrate (200 mg/day, n = 40), or a combination of both (atorvastatin 20 mg/day plus fenofibrate 200 mg/day, n = 40). The effect of treatment on LDL cholesterol, triglycerides (TGs), HDL cholesterol, apolipoprotein A-I and B, lipoprotein(a), and plasma fibrinogen (PF) was recorded. Moreover, the percentage of patients that reached the American Diabetes Association treatment goals and the estimated CAD risk status were calculated. RESULTS: No patient was withdrawn from the study because of side effects. The atorvastatin-fenofibrate combination reduced total cholesterol by 37%, LDL cholesterol by 46%, TGs by 50%, and PF by 20%, whereas it increased HDL cholesterol by 22% (P < 0.0001 for all). These changes were significantly better than those of both monotherapies. Of the patients on drug combination, 97.5% reached the LDL cholesterol treatment goal of <100 mg/dl, 100% reached the desirable TG levels of <200 mg/dl, and 60% reached the optimal HDL cholesterol levels of >45 mg/dl. These rates were significantly higher than those of both monotherapies. Combined treatment reduced the 10-year probability for myocardial infarction from 21.6 to 4.2%. CONCLUSIONS: The atorvastatin-fenofibrate combination has a highly beneficial effect on all lipid parameters and PF in patients with type 2 diabetes and CHL. It improved patients' CAD risk status significantly more than each drug alone.     

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.     

Low-density lipoprotein apheresis for prevention and regression of atherosclerosis: clinical results.

Hypercholesterolemia can be adequately controlled by appropriate diet and maximum lipid lowering drug therapy in most patients. Nevertheless, there exists a group of patients, including those with familial hypercholesterolemia (FH), who remain at high risk for the development or progression of premature coronary heart disease (CHD). For these patients additional measures such as surgery and low-density lipoprotein (LDL) apheresis have to be considered. The objective of this multicenter trial, which included 30 clinical centers (28 in Germany and one each in Scotland and Luxembourg), was to determine if repeated LDL apheresis using the Liposorber LA-15 system (Kaneka Corporation, Osaka, Japan) could lead to an additional acute and time averaged lowering of total cholesterol (TC) and LDL-cholesterol (LDL-C) in severely hypercholesterolemic patients whose cholesterol levels could not be controlled by appropriate diet and maximum drug therapy. A total of 6,798 treatments were performed on 120 patients, including 8 with homozygous FH, 75 with heterozygous FH, and 37 with unclassified FH or other hyperlipidemias from 1988 through 1994. The mean TC and mean LDL-C levels at baseline were 410.0 mg/dl and 333.9 mg/dl, respectively. LDL apheresis was performed once a week or at least once every 2 weeks in all patients. During treatment with the Liposorber system the mean acute percentage reduction was 52.6% for TC and 63.1% for LDL-C. Very low density lipoprotein cholesterol (VLDL-C) and triglycerides (TG) were also substantially reduced to 60.6% and 47.5%, respectively. Fibrinogen, a potential risk factor for CHD, was reduced by 26.2%. In contrast, the mean acute reduction of high density lipoprotein (HDL) was only 3.4%. During the course of the treatment, the time averaged levels of TC and LDL-C were reduced by approximately 39% and 50%, respectively, compared to baseline levels. The adverse events (AEs) were those generally associated with extracorporeal treatments. The most common AE was hypotension, with 69 episodes corresponding to 1% of all treatments reported in 44 of the 120 patients treated. All other kinds of AEs occurred in less than 0.2% of the treatments. The treatment with the Liposorber LA-15 system was overall well tolerated. It should be noted, however, that a more severe type of hypotensive reaction associated with flush, bradycardia, and dyspnea was reported in patients taking concomitant angiotensin converting enzyme (ACE) inhibitor medication. Except for such anaphylactoid-like reactions associated with the intake of ACE inhibitors, the Liposorber LA-15 system represents a safe and effective therapeutic option for patients suffering from severe hypercholesterolemia that could not be adequately controlled by diet and maximum drug therapy.