Efficacy and tolerability of lovastatin in hypercholesterolemic women.

In a previous report of a multicenter study (Kannel et al, 1990), the results of 6 months' treatment with lovastatin in 489 adults with primary hypercholesterolemia were presented. The present report contains the results from the 236 women patients. The intial dose of lovastatin was 20 mg daily and could be increased to a maximum of 80 mg/day. At the end of 1 month of treatment, levels of total cholesterol, low-density lipoprotein (LDL) cholesterol, very-low-density lipoprotein cholesterol, triglycerides, and the total cholesterol:high-density lipoprotein (HDL) cholesterol and LDL:HDL cholesterol ratios were significantly lower and the HDL cholesterol levels were significantly higher. These improvements in the lipid profile were maintained for 6 months. The results in the 88 women aged 65 to 83 years and in the 147 women aged 25 to 64 years were similar. LDL-cholesterol goals of less than 3.36 mmol/L in patients with coronary heart disease (CHD) or two or more CHD risk factors and less than 4.14 mmol/L among the other patients were achieved by 48% of the women at 1 month and 58% by 6 months. At least one adverse effect was reported by 18% of the women, the most common being abdominal pain, diarrhea, and constipation. The results indicate that hypercholesterolemic women respond well to treatment with lovastatin.     

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.     

Effect of lovastatin on serum lipids in patients with nonfamilial primary hypercholesterolemia

The effect of lovastatin on serum lipids and its tolerability in patients with non-familial primary hypercholesterolemia (type II-A and type II-B) during a six-month period were evaluated in this open-label study. Thirty-eight patients were enrolled in the study; tolerability was assessed in all 38 patients. Thirty patients completed the study, and the effect of lovastatin on serum lipids in these patients was assessed. Some patients had been treated for hypercholesterolemia with long-term dietary and other non-pharmacologic means before entry into the study. All patients were unresponsive to a six-week program of intensive dietary therapy and other nonpharmacologic treatment to lower their blood cholesterol levels before receiving lovastatin. While maintaining intensive dietary therapy, administration of lovastatin was instituted at a dosage of 20 mg/day, which was increased by 20-mg increments monthly, as necessary, to a maximum of 80 mg/day. In an effort to achieve goal levels of low-density lipoprotein cholesterol (LDL-C), ten patients received a daily dosage of 20 mg, 12 patients received 40 mg, seven patients 60 mg, and one patient 80 mg. Twenty-nine of the 30 patients achieved significant lowering of serum levels of total cholesterol (TC), LDL-C, and apolipoprotein (apo) B-I; this was demonstrated after the first month of therapy with lovastatin and was maintained throughout the six-month treatment period. One patient failed to demonstrate lowering of these serum lipids, despite receiving the maximum recommended dosage of lovastatin of 80 mg/day. Comparative measurements of serum lipids during dietary therapy alone and after six months of diet plus lovastatin therapy were as follows: TC, 289 +/- 5 versus 216 +/- 9 mg/dl (P less than 0.0005); LDL-C, 206 +/- 4 versus 141 +/- 5 mg/dl (P less than 0.0005); and apo B-I, 112 +/- 3 versus 89 +/- 2 mg/dl (P less than 0.0005). Serum levels of very-low-density lipoprotein cholesterol (VLDL-C) and triglycerides decreased slightly during lovastatin therapy, but the changes were not statistically significant. There were slight but statistically insignificant increases in serum levels of high-density lipoprotein cholesterol (HDL-C), apo A-I, and apo A-II.(ABSTRACT TRUNCATED AT 400 WORDS)     

老年人冠心病危险因素分析

目的　综合评价冠心病危险因素对老年人冠心病的影响。方法　对 35 7例行选择性冠状动脉造影检查的老年患者进行回顾性分析。结果　 35 7例行冠状动脉造影检查的患者中确诊冠心病 2 32例 ,阳性率 6 5 4%。单因素分析 ,增龄、男性、吸烟、饮酒、高血压、糖尿病、体重增加、总胆固醇及低密度脂蛋白升高、高密度脂蛋白降低易致老年冠心病事件发生。多因数回归分析 ,性别、年龄、吸烟及LDL/HDL C为冠心病事件发生的独立危险因素。结论　与年轻患者比较老龄患者的心血管事件发生的危险性更高。因此对危险因素的预防和控制可为老龄患者带来的绝对获益更大。     

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.     

Asessing coronary heart disease risk and managing lipids.

Elevated low-density lipoprotein (LDL) and below normal high-density lipoprotein (HDL) cholesterol are risk factors for coronary heart disease (CHD). According to clinical guidelines, LDL cholesterol is the primary target for lipid-altering therapy. Many patients who develop CHD have LDL and HDL cholesterol levels that fall within the desirable or low-risk category; consequently, conventional measurements of plasma lipids may not accurately detect high-risk patients. This article discusses the clinical significance of lipoprotein subclasses and methods of measurement. Assessing lipoprotein subclasses provides a more comprehensive and efficacious therapeutic approach compared with the standard lipid profile.     

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)     

Comparison of the effects of guanabenz and hydrochlorothiazide on plasma lipids

The effects of hydrochlorothiazide (HCTZ) and guanabenz monotherapy on blood pressure and serum lipoprotein levels were compared in a 14-week, randomized, parallel, double-blind multicenter study of 218 outpatients with mild hypertension. Mean supine blood pressure decreased 13/9 mm Hg in the guanabenz group and 17/11 mm Hg in the HCTZ group, changes that were significantly (p less than 0.01) different from baseline but not significantly different between the two treatment groups. Significant (p less than 0.01) mean decreases in total cholesterol and low-density lipoprotein (LDL) cholesterol levels (of 9 mg/dl and 4 mg/dl from baseline values) occurred during guanabenz treatment; HDL cholesterol levels fell by an average of 4 mg/dl. In the HCTZ group, triglyceride levels were significantly (p less than 0.01) increased by 13 mg/dl, and HDL cholesterol levels fell by 2 mg/dl. The change in LDL cholesterol levels, but not HDL cholesterol levels, was significantly different between guanabenz and HCTZ periods. The results show that guanabez, although providing effective blood pressure control that is comparable to that of HCTZ, has more favorable effects on lipoproteins.     

High-density lipoproteins in cholesterosis of the gall bladder

The composition of serum high-density lipoproteins (HDL) was studied in 64 patients with polypous cholesterosis (PC). The spectrum of serum lipids in patients with PC was characterized by the lower concentrations of HDL cholesterol (42.0 +/- 2.5 mg/dl; p < 0.05) and higher concentrations of low-density lipoproteins (LDL) cholesterol (169.9 +/- 6.9 mg/dl; p < 0.01) than those in the controls. The decreased HDL cholesterol, or hypoalphacholesterolemia was associated with quantitative changes in HDL phospholipids (PL) (66.48 +/- 3.4; p < 0.01) and with changes in the composition of individual PL by lowering the proportion of lecithin (47.13 +/- 2.19 mg/dl; p < 0.01). It may be suggested that the lower amount of HDL cholesterol is caused by the decreased HDL acception of free cholesterol from the peripheral cell membranes due to the impaired complexation of PL with free cholesterol and associated the altered PL composition of the superficial monolayer of a lipoprotein particle. At the same time the physicochemical changes in Hdl superficial layer are a cause of abnormal free cholesterol esterification and the impaired plunge of esterified cholesterol into the nucleus of a HDL particle, which facilitates the conversion of HDL to LDL and may explain elevated LDL levels in cholesterosis. The findings suggest that serum lipids are involved in the development of cholesterosis.     

The evolution and revolution of the implantable cardioverter defibrillator

A low-density lipoprotein (LDL) cholesterol goal of less than 100 mg/dl is recommended for patients at moderate to high risk of cardiovascular disease with an optional LDL goal of less than 70 mg/dl for patients at a very high risk of cardiovascular disease. Most patients will require reductions in LDL of more than 50% in order to achieve these more aggressive goals. Only a few agents will lower LDL by at least 50%. This review will focus on the efficacy and safety ezetimibe/simvastatin coadministered as a therapy with enhanced LDL-lowering efficacy, while minimizing the adverse effects of statins in a wide range of patients. Ezetimibe 10 mg/simvastatin 80 mg lowers LDL by approximately 60% and has been demonstrated to be superior to the highest doses of atorvastatin and rosuvastatin for lowering LDL and raising high-density lipoprotein.     

Combination therapy with ezetimibe and simvastatin to achieve aggressive LDL reduction

A low-density lipoprotein (LDL) cholesterol goal of less than 100 mg/dl is recommended for patients at moderate to high risk of cardiovascular disease with an optional LDL goal of less than 70 mg/dl for patients at a very high risk of cardiovascular disease. Most patients will require reductions in LDL of more than 50% in order to achieve these more aggressive goals. Only a few agents will lower LDL by at least 50%. This review will focus on the efficacy and safety ezetimibe/simvastatin coadministered as a therapy with enhanced LDL-lowering efficacy, while minimizing the adverse effects of statins in a wide range of patients. Ezetimibe 10 mg/simvastatin 80 mg lowers LDL by approximately 60% and has been demonstrated to be superior to the highest doses of atorvastatin and rosuvastatin for lowering LDL and raising high-density lipoprotein.     

Comparison of ultracentrifugation and a precipitation method for high-density lipoprotein cholesterol quantitation in insulin-dependent diabetic patients

We compared sodium phosphotungstic acid and magnesium chloride precipitation method for high-density lipoprotein (HDL) cholesterol quantitation with the ultracentrifugation method in 64 insulin-dependent diabetic patients with plasma triglyceride less than 3 mmol/l. The cholesterol content of HDL after precipitation of very-low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) was 86% +/- 3% of the cholesterol content of HDL (q greater than 1.063) determined after ultracentrifugation at q = 1.063 (1.33 +/- 0.05 mmol/l vs 1.55 +/- 0.06 mmol/l; p less than 0.001). HDL cholesterol determined after precipitation closely correlated to HDL cholesterol determined after ultracentrifugation (r = 0.97; p less than 0.001). The absolute difference between the HDL cholesterol values obtained by the two methods was correlated to HDL cholesterol (ultracentrifugation) (r = 0.75; p less than 0.001), but it was not correlated to VLDL cholesterol, LDL cholesterol, triglyceride, HbA1c, blood glucose or serum albumin. LDL cholesterol calculated by use of Friedewald's formula was 108% +/- 4% of the cholesterol content of LDL (q = 1.019 to 1.063), determined after ultracentrifugation, but the calculated and the ultracentrifugally determined LDL cholesterol values were closely correlated (r = 0.98; p less than 0.001). These results suggest that during sodium phosphotungstic acid and magnesium chloride precipitation of plasma from diabetic patients, a constant fraction of HDL cholesterol is co-precipitated, resulting in a systematic difference in HDL cholesterol quantitation when compared with the ultracentrifugation method.     

Lack of effect of lovastatin therapy on the parameters of whole-body cholesterol metabolism.

The effects of lovastatin therapy on the parameters of body cholesterol metabolism were explored in nine hypercholesterolemic patients. Long-term cholesterol turnover studies were performed before therapy, and were repeated after 15 mo of lovastatin therapy (40 mg/d) while continuing on therapy. The major question addressed was whether a reduction in plasma cholesterol level with lovastatin would be associated with a reduction in the whole-body production rate of cholesterol or with the sizes of exchangeable body cholesterol pools as determined by the three-pool model of cholesterol turnover. The mean plasma cholesterol level decreased 19.4% (from 294 to 237 mg/dl), and low-density lipoprotein cholesterol decreased 23.8% (from 210 to 159 mg/dl) with lovastatin therapy. Changes in high-density lipoprotein cholesterol level were not significant. The cholesterol production rate did not change significantly with therapy (1.09 +/- 0.10 [mean +/- S.D.] vs. 1.17 +/- 0.09 g/d). By comparison, colestipol and niacin treatment in three other subjects more than doubled the cholesterol production rate (1.14 +/- 0.28 vs. 2.42 +/- 0.34 g/d). Thus, hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibition by lovastatin at the therapeutic dose used here did not change the steady-state rate of whole-body cholesterol synthesis. Despite the changes in plasma cholesterol levels, no significant changes were seen in the values of M1, of M3 or of Mtot, the sizes of the pools of rapidly, of slowly, and of total body exchangeable cholesterol. Conclusion: lovastatin therapy to lower plasma cholesterol does not lead to corresponding reductions in body cholesterol pools or to a reduction in the rate of whole-body cholesterol synthesis. In the new steady state that exists during long-term lovastatin therapy, along with increased expression of the genes for HMG-CoA reductase and the LDL receptor, the body compensates for the effects of the drug so that cholesterol production rate and tissue pool sizes are not changed from pretreatment values.     

A crossover comparison of the efficacy and safety of lovastatin and gemfibrozil in the treatment of hyperlipidemic organ transplant recipients.

Hypercholesterolemia is associated with accelerated atherosclerosis in transplant recipients. It has been notoriously difficult to treat pharmacologically due to the complex interactions that occur with lipid-lowering drugs and immunosuppressive therapies. The purpose of the current study was to compare the efficacy and safety of a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (lovastatin, 20 mg/d) with a fibric acid derivative (gemfibrozil, 600 mg twice a day). We used a randomized, crossover design in 18 solid organ transplant recipients who followed the National Cholesterol Education Program Adult Treatment Guidelines diet for 8 weeks and had persistent elevations of total cholesterol (>240 mg/dL). Each patient received each therapy for a minimum of 8 weeks (mean 14.2 +/- 2.4, range 8-20 weeks). The participants had stable allograft function and were treated with a standard immunosuppressive regimen containing cyclosporine, prednisone, and azathioprine. Lovastatin therapy reduced the mean total cholesterol by 15.5% (271.9 mg/dL to 229.9 mg/dL; p = 0.02) and the mean low-density lipoprotein (LDL) cholesterol by 22.7% (178.2 mg/dL to 137.8 mg/dL; p = 0.07). There were no significant changes in high-density lipoprotein (HDL) cholesterol or triglycerides. Conversely, when these same patients were treated with gemfibrozil, the mean total cholesterol decreased by 7.9% (271.9 mg/dL to 250.5 mg/dL; p = NS) and the LDL cholesterol decreased by 5.1% (178.2 mg/dL to 169.1 mg/dL; p = NS). In addition, the mean triglyceride concentration decreased significantly by 46.1% (234.0 mg/dL to 126.3 mg/dL; p = 0.002) and the mean HDL cholesterol increased 15.4% (48.8 mg/dL to 56.3 mg/dL; p = 0.09). In all patients, the serum creatinine, hepatocellular enzymes, and creatinine phosphokinase remained stable. Lovastatin was discontinued in three patients for myalgias, one patient with unexplained anemia, and one patient with parasthesias. These results suggest that lovastatin and gemfibrozil are both safe and efficacious in transplant patients. However, neither therapy alone completely corrects abnormalities of high LDL cholesterol and low HDL cholesterol in transplant recipients.     

Lipoprotein composition and HDL particle size distribution in women with non-insulin-dependent diabetes mellitus and the effects of probucol treatment

To further characterize the spectrum of potentially atherogenic disturbances in lipoprotein composition in non-insulin-dependent diabetes mellitus (NIDDM), we have studied a subset of women with NIDDM before and after treatment with the lipophilic lipid-lowering drug probucol (1 gm day), which we have shown corrects certain compositional abnormalities these women share with subjects who have hypercholesterolemia. Before treatment, the NIDDM group had a somewhat higher plasma triglyceride level (154 +/- 58.3 mg/dl, vs control, 80.0 +/- 21 mg/dl [mean +/- SD]; p less than 0.025) than controls but their cholesterol and high-density lipoprotein cholesterol (HDL-C) levels did not differ from control levels. A number of significant disturbances, however, were present in the surface and core lipid composition of their lipoproteins. Although the cholesterol content of NIDDM low-density lipoprotein (LDL) was similar to that of controls, its content of sphingomyelin and phosphatidylinositol plus phosphatidylserine and sphingomyelin-to-lecithin ratio all were significantly reduced. Moreover, their very-low-density lipoprotein (VLDL) and HDL2 tended to have reduced amounts of free (unesterified) cholesterol (FC) relative to lecithin, and their HDL2 and HDL3 tended to be triglyceride enriched. Probucol therapy resulted in significant decreases in total plasma cholesterol (-15%), FC (-28%), HDL-C (-22%), and triglyceride (-16%) and in apoproteins A-I, B, and E (apo A-I, B, and E), without changing diabetic control (before probucol: hemoglobin A1, cholesterol, 10.7% +/- 2.7%; after probucol: 10.9% +/- 3.0%).(ABSTRACT TRUNCATED AT 250 WORDS)     

Primate model for the study of hepatic metabolism of lipoprotein cholesterol

We describe a primate model for the study of net cholesterol flux by splanchnic, portal, and hepatic regions concomitant with that of biliary lipid secretion in conscious healthy fed or fasting baboons with exteriorized but physiologically intact enterohepatic circulations. In five fasting baboons studied, we found evidence for low-density lipoprotein (LDL) cholesterol uptake by the liver of 1.0 mg/min, P less than 0.05. Conversely, splanchnic production of LDL cholesterol was found in the fed state (n = 5), amounting to 0.8 mg/min, P less than 0.05. Uptake or secretion of high-density lipoprotein (HDL) cholesterol by either the liver or the intestine could not be detected by transgradient analysis in our animals in either fed or fasting states. Very low-density lipoprotein secretion of 0.4 mg/min by the liver was also found in the fed state. Isotopic biliary cholesterol derived from labeled plasma HDL or LDL cholesterol reflected hepatic LDL cholesterol production in the fed state but LDL cholesterol uptake in the fasting state. Biliary cholesterol secretion amounted to 8.5% of net hepatic lipoprotein cholesterol flux in the fed state and 10% in the fasting state. We conclude that uptake of LDL cholesterol by the liver is appreciable and contributes to biliary sterol secretion in the fasting baboon. Uptake or secretion of HDL cholesterol was not detected in any metabolic beds by transgradient analysis, but in tracer studies appeared to be a major source of lipoprotein cholesterol transferred to bile in the fed state.     

Lipoproteins and apolipoproteins in human pleural effusions.

We investigated the lipoproteins and apoproteins in human serum and pleural effusions of different origin: transudates, inflammatory exudates, and malignant exudates. Transudates had a low cholesterol content of 35 +/- 12 mg/dl (mean +/- SD) because of low levels of low-density lipoprotein (LDL) cholesterol--representing 16% of serum levels--whereas inflammatory exudates (cholesterol 92 +/- 26 mg/dl) and malignant exudates (cholesterol 86 +/- 6 mg/dl) exhibited high levels of LDL, with 67% and 69% of serum levels. Apolipoprotein (apo) B level corresponded with LDL and presented with multiple split-products in sodium dodecyl sulfate-polyacrylamide gel electrophoresis in exudative effusions. LDL levels in effusions correlated with serum levels in exudates but did not correlate with those in transudates. In contrast, lipoprotein(a) appeared in all effusions from patients with detectable serum levels. The isoforms were similar as demonstrated by immunoblotting. Differences were found in the composition of the high-density lipoprotein (HDL) fraction: transudates had cholesterol-rich HDL when compared with serum. HDL particles of malignant exudates were poor in cholesterol, and isoelectric focusing demonstrated more sialized apolipoprotein E. A strongly abnormal HDL level with accumulation of cholesterol was found in a long-standing tuberculous effusion. In conclusion, cholesterol in acute effusions is bound to lipoproteins and derived from the blood. The difference in total cholesterol levels between transudates and exudates is based on the lack of LDL in transudates. Transudates show the lipoprotein characteristics of interstitial fluid. Alterations of lipoproteins occur in chronic inflammation and in malignancy with possible de novo synthesis of apolipoprotein E by tumor cells. Lipoprotein(a) accumulates independently from LDL in the pleural space, a finding that supports the view that the physiologic function of lipoprotein(a) is located in the interstitial space.     

Comparison of cholesterol-lowering regimens

Drug therapy should be reserved for patients with marked total cholesterol elevation not amenable to dietary measures. While current guidelines suggest that bile acid sequestrants, such as cholestyramine and colestipol, are first-line drugs for the treatment of hypercholesterolemia, recent studies suggest that lovastatin is a safe, more potent alternative. Gemfibrozil reduces the serum triglyceride level and raises the high-density lipoprotein (HDL) cholesterol level, but has only a moderate effect on the serum cholesterol level. Nicotinic acid lowers serum low-density lipoprotein (LDL) cholesterol and triglyceride levels and raises serum HDL levels, but its use is limited because of troublesome side effects, notably a flushing reaction. Probucol lowers both serum LDL and HDL levels and is a second-line agent for the treatment of hypercholesterolemia.     

Effect of lovastatin on lipoprotein fluidity in patients with hypercholesterolaemia.

Lovastatin was administered to six hypercholesterolaemic patients (mean plasma cholesterol 450 mg dl-1). Plasma lipoproteins (VLDL, LDL, and HDL) were separated before and following 7 and 12 weeks treatment with lovastatin. Fluidity was quantified by fluorescence polarization measurements using 1,6-diphenyl 1,3,5 hexatriene (DPH) as the fluorescent probe. Lovastatin treatment resulted in a significant reduction of total plasma cholesterol, LDL cholesterol and VLDL cholesterol (-41%, -44%, -68%, respectively). Fluidity measurements showed significant (p < 0.01) increase in LDL fluidity by 11% and 21% after 7 and 12 weeks of lovastatin treatment, whereas, VLDL fluidity was increased by 27% after 12 weeks of therapy. HDL fluidity was not altered. These alterations in the fluidity of the atherogenic lipoproteins (LDL and VLDL) in hypercholesterolaemic patients may prove to be of significance in reducing the risk of atherosclerosis.     

Identifying patients at risk for coronary heart disease: implications from trials of lipid-lowering drug therapy

Abnormal lipid levels contribute significantly to the risk of coronary heart disease (CHD), which is increased further in the presence of other risk factors. The association between elevated low-density lipoprotein (LDL) cholesterol and CHD risk is well established, and large primary and secondary prevention studies of HMG-CoA reductase inhibitors (statins) have shown conclusively that lowering LDL cholesterol levels reduces CHD events and total mortality. Regardless of the intervention used (diet, surgery, drugs), reduction of plasma cholesterol has consistently produced a reduction in cardiovascular risk. Absolute benefit is greatest in those who are at highest risk initially, and trial results suggest that the lower the LDL cholesterol level achieved, at least down to LDL of 3.0 mmol/l, then the lower is the CHD event risk. Epidemiological data also point to the negative impact of other lipids on CHD risk. Low levels of high-density lipoprotein (HDL) and high levels of triglycerides (particularly in conjunction with an LDL/HDL ratio >5) are particularly strong risk factors for CHD. Thus, although prevention trials to date have primarily assessed the impact of LDL lowering on CHD events, the initial assessment of CHD risk should consider a more detailed atherogenic profile including HDL and triglyceride levels. A general approach to preventing cardiovascular disease should include strategies to reduce the overall CHD risk by lifestyle modification and management of modifiable risk factors such as smoking, hypertension and diabetes. Based on data from recent prevention studies, and because they are the most potent lipid-lowering agents available for lowering LDL cholesterol, statins have appropriately become the drug of choice for most patients with hyperlipidaemia who require drug therapy.