Israel Medical Association Journal

Background: Elevated fibrinogen levels are considered a risk factor for the development of atherosclerosis and might be used as a predictor of risk for the development of atherothrombotic events. Several studies have reached equivocal conclusions regarding the effect of statins on fibrinogen.

Objectives: To evaluate the effect of atorvastatin on plasma fibrinogen levels in patients with severe hypercholesterolemia and no other risk factors.

Methods: Twenty-two patients with low density lipoprotein-cholesterol levels above 170 mg/dl (4.40 mmol/L) and with no other risk factors were included in the study. None of the patients had ever received hypolipidemic medication. Patients were followed for 24 weeks (6 office visits 4 weeks apart). During office visits, lipid profile, complete blood count, fibrinogen and C-reactive protein levels were measured.

Results: After 24 weeks of follow-up, total cholesterol decreased by 33% (287 ± 10 to 192 ± 8 mg/dl, P < 0.001), LDL-C[1] by 45% (198 ± 8 to 111 ± 7 mg/dl, P < 0.001) and triglycerides by 21% (189 ± 26 to 138 ± 15 mg/dl, P <0.001). Fibrinogen levels dropped by 18% (355 ± 26 to 275 ± 7 mg/dl, P = 0.01). CRP[2] levels decreased from 0.51 ± 0.15 to 0.28 ± 0.10 mg/dl, but the difference was not statistically significant (P = 0.09). High density lipoprotein, hemoglobin, white blood cell and platelet counts did not change.

Conclusions: We found that atorvastatin reduces plasma fibrinogen in patients with hypercholesterolemia.

Background: The beneficial effect of 3-hydroxy-3-methylglutyaryl co-enzyme A reductase inhibitors on cardiovascular risk reduction has been clearly established. Concerns have been raised that lowering blood cholesterol by other hypolipidemic drugs or by a non-pharmacologic approach may have deleterious effects on psychopathologic parameters. Garlic is one of the most commonly used herbal remedies and is considered to have hypocholesterolemic as well as other cardio-protective properties. Its effect on psychopathologic parameters has never been reported.

Objectives: To evaluate the effect of garlic on lipid parameters and depression, impulsivity, hostility and temperament in patients with primary type 2 hyperlipidemia.

Methods: In a 16 week prospective double-blind placebo-controlled study, 33 patients with primary hypercholesterolemia and no evidence of cardiovascular disease were randomly assigned to receive either garlic or placebo. Garlic in the form of alliin 22.4 mg/day was given to 13 patients, and placebo to 20. Both groups received individual dietary counseling. The changes in lipid profile and the various psychopathologic parameters were determined at the beginning and end of the trial. The differences in lipid parameters were evaluated by Student’s t-test. The psychological data were analyzed by one-way analysis of variance (ANOVA) with repeated measures and Neuman-Keuls test.

Results: No significant changes were observed in levels of total cholesterol, low density lipoprotein-cholesterol, high density lipoprotein-cholesterol and triglycerides, or in the psychopathologic parameters evaluated.

Conclusion: Short-term garlic therapy in adults with mild to moderate hypercholesterolemia does not affect either lipid levels or various psychopathologic parameters.

Background: Decreased elasticity of the aorta is associated with aging and several risk factors of atherosclerosis. The data regarding this phenomenon in patients with familial hypercholesterolemia are rather sparse.

Objectives: To evaluate non-invasively the elasticity of the proximal ascending aorta of 51 heterozygous FH[1] patients compared to 42 normal age and gender-matched controls.

Methods: Aortic elasticity was estimated by transthoracic echocardiography using the “pressure-strain” elastic modulus and aortic strain formulas.

Results: The elastic modulus score was higher in the FH group than in the controls (1.12 ± 0.91 10⁶ dynes/cm² vs. 0.65 ± 0.46 10⁶ dynes/cm² respectively, P = 0.01). This was consistent in both the pediatric (0.5 ± 0.2 10⁶ dynes/cm² vs. 0.4 ± 0.1 10⁶ dynes/cm² respectively, P = 0.009) and adult subgroups (1.3 ± 1.0 10⁶ dynes/cm² vs. 0.8 ± 0.5 10⁶ dynes/cm² respectively, P = 0.0004). Aortic strain was significantly lower in patients with FH than in controls (6 ± 4% vs. 9 ± 5% respectively, P = 0.0002). These findings reflected decreased elasticity of the proximal ascending aorta in the FH patients. In multivariate analysis, age, serum cholesterol level and serum triglycerides level were the independent predictors of the elastic modulus score, whereas age was the predictor of aortic strain.

Conclusions: The elasticity of the proximal ascending aorta is decreased in heterozygous FH patients.

Background: Low density lipoprotein apheresis is used as a complementary method for treating hypercholesterolemic patients who cannot reach target LDL[1]-cholesterol levels on conventional dietary and drug treatment. The DALI system (direct absorption of lipoproteins) is the only extracorporeal LDL-removing system compatible with whole blood.

Objective: To describe our one year experience using the DALI[2] system.

Methods: LDL apheresis was used in 13 patients due to inability to reach target LDL-C levels on conventional treatment. They included seven patients with familial hypercholesterolemia, three who had adverse reactions to statins, and three patients with ischemic heart disease who did not reach LDL-C target level on medical treatment.

Results: The average triglyceride, total cholesterol, high density lipoprotein-C and LDL-C levels before and after treatment in all patients were: 170 ± 113 vs. 124 ± 91, 269 ± 74 vs. 132 ± 48, 42 ± 8 vs. 37 ± 7.9, and 196 ± 77 vs. 80 ± 52 mg/dl, respectively. Comparing the results of a subgroup of seven patients who had previously been treated with plasma exchange, it is noteworthy that while the reduction in triglyceride, total cholesterol and LDL-C are comparable, the effect on HDL[3]-C concentration was less apparent: from an average of 39.7 ± 8.7 and 23 ± 5.7 mg/dl before and after plasma exchange to an average of 43.9 ± 8.1 and 38.4 ± 7 mg/dl before and after LDL apheresis, respectively. Five patients developed treatment-related adverse events: three experienced allergic reactions manifested as shortness of breath, urticaria and facial flushing; one patient developed rhabdomyolysis, an adverse reaction that was not reported previously as a result of LDL apheresis; and one patient had myopathy with back pain. All untoward effects occurred during the first few treatment sessions.

Conclusions: LDL apheresis using the DALI system is highly efficacious for the treatment of hypercholesterolemia. It is associated with a significant number of side effects occurring during the first treatment sessions. In patients not experiencing adverse effects in the early treatment period, it is well tolerated, and can provide remarkable clinical benefit even after short-term therapy.

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Background: Hyperlipidemia is a major risk factor for coronary heart disease. Reducing low density lipoprotein-cholesterol can significantly reduce the risk of CHD[1], but many patients fail to reach the target LDL-C[2] goals due to low doses of statins or low compliance.

Objectives: To treat high risk patients with atorvastatin in order to reach LDL-C goals (either primary or secondary prevention) of the Israel Atherosclerosis Society.

Methods: In this open-label study of 3,276 patients (1,698 of whom were males, 52%), atorvastatin 10 mg was given as a first dose, with follow-up and adjustment of the dose every 6 weeks. While 1,670 patients did not receive prior hypolipidemic treatment, 1,606 were treated with other statins, fibrates or the combination of both.

Results: After 6 weeks of treatment, 70% of the patients who did not receive prior hypolipidemic medications and who needed primary prevention reached target LDL-C levels. Interestingly, a similar number of patients on prior hypolipidemic treatment reached the LDL-C goals for primary prevention. The patients treated with other statins, fibrates or both did not reach the LDL-C treatment goals. Only 34% of all patients who needed secondary prevention reached the ISA[3] LDL-C target of 100 mg/dl. Atorvastatin proved to be completely safe; only two patients had creatine kinase elevation above 500 U/L, and another six had mild CK[4] elevation (<500 U/L). None of the patients had clinical myopathy, and only one had to be withdrawn from the study.

Conclusion: Atorvastatin is a safe and effective drug that enables most patients requiring primary prevention to reach LDL-C goal levels, even with a low dose of 10 mg. Patients in need of secondary prevention usually require higher doses of statins.

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Background: Case-control and prospective studies indicate that an elevated plasma homocysteine level is a powerful risk factor for atherosclerotic vascular diseases. Certain medications can induce hyperhomocystinemia, such as methotrexate, trimethoprim and anti-epileptic drugs. There are few reports indicating an interaction between lipid-lowering drugs (cholestyramine and niacin) and homocysteine. Recently, an interaction was shown between fenofibrate and benzafibrates (a fibric acid derivative) and homocysteine plasma levels.

Objectives: To evaluate the effects of different fibrates on plasma homocysteine levels and to measure the reversibility of this effect.

Methods and Results: We investigated the effects of ciprofibrate and bezafibrate on homocysteine levels in patients with type IV hyperlipidemia and/or low high density lipoprotein levels. While a 57% increase in homocysteine was detected in the ciprofibrate-treated group (n=26), a 17% reduction n homocysteine was detected in the group treated with bezafibrate (n=12). The increase in homocysteine in the ciprofibrate-treated group was sustained for the 12 weeks of treatment and was partially reversible after 6 weeks of discontinuing the ciprofibrate therapy.

Conclusions: These results indicate that an increase In plasma homocysteine levels following administration of flbrates is not a class effect, at least in its magnitude. Moreover, it is reversible upon discontinuation of the treatment.
 

Background: The degree to which serum total cholesterol predicts cariovascular disease is uncertain. While most authors have placed TC among the most powerful risk indicators of CVD, some have claimed that it predicted CVD in women only, or even not at all.

Objective: To determine the predictive value of serum total cholesterol relative to diabetes, smoking, systolic blood pressure and body mass index (kg/m2), for cardiovascular disease mortality in 3,461 occupationally active Israeli males.

Methods: A prospective follow-up was carried out for the years 1987-1998 to determine the effect of age, smoking habits, a history of diabetes, SBP, BMI and TC, at entry, on CVD mortality.

Results: There were 84 CVD deaths during a total of 37,174 person-years follow up. The hazard ratios (95% confidence intervals) for CVD mortality with respect to variables at entry were: diabetes 5.2 (2.1-13.2), age 2.2 (1.7-2.9), smoking 1.3 (1.0-1.8), SBP 1.4 (1.1-2.0), TC 1.5 (1.0-2.1) and BMI 1.2 (0.7-2.2). Among non-obese, non-diabetic, normotensive subjects the hazard ratio of TC adjusted for age and smoking was 1.16 (1.09-1.22) per 10 mg/dl. In the remaining subjects it was 1.04 (0.98-1.12) only. There was a significant interaction between TC and diabetes, hypertension or obesity (P=0.003).

Conclusions: In this population of Israeli males we found an interaction between TC and other risk indicators for CVD. Confirmation is required for the unexpected finding that the predictive value of TC for CVD mortality among non-diabetic, non-obese and normotensive subjects exceeded that among subjects with either of these risk factors.