Israel Medical Association Journal

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 None of the patients had clinical myopathy, and only one had to be withdrawn from the study.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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The complex genetic nature of many common diseases makes the identification of the genes that predispose to these ailments a difficult task. In this review we discuss the elements that contribute to the complexity of polygenic diseases and describe an experimental strategy for disease-related gene discovery that attempts to overcome these factors. This strategy involves a population-based case-control paradigm and makes use of a highly informative, homogeneous founder population, many of whose members presently reside in Israel. The properties of single nucleotide polymorphisms, which are presently the markers of choice, are discussed, and the technologies that are currently available for SNP[1] genotyping are briefly presented.

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[1] SNP = single nucleotide polymorphism

Background: Clinical studies showing an association between immigration and increased prevalence of coronary risk factors or mortality rate in patients immigration is associated with greater risk among immigrants from the Soviet with coronary artery disease are scarce.

Objectives: To compare the risk profile and mortality of coronary patients born in Israel with those who immigrated to Israel, and to determine whether recent Union.

Methods: Demographic, clinical, and laboratory data were collected on chronic coronary artery disease patients from 18 Israeli medical centers during the screening period of the Bezafibrate Infarction Prevention Study in the early 1990s. Data on mortality after a mean 7.7 year follow-up were obtained from the Israel Population Registry.

Results: While significant differences in mortality (14.7% vs. 18.5%, P < 0.001) were observed between Israeli-born patients and immigrants respectively, the mortality in these groups was similar when compared within specific age groups. Immigrants suffered more from hypertension and angina pectoris, and their New York Heart Association functional limitation class was higher, as compared to their Israeli-born counterparts. A multivariate analysis of mortality comparing patients from the Soviet Union who immigrated after 1970 with those who immigrated before 1970 showed an increased risk for newer immigrants, with a hazard ratio of 1.69 (95% confidence interval 1.19-2.40) for those immigrating between 1970 and 1984, and 1.68 (95% CI[1] 1.01-2.28) for those immigrating between 1985 and 1991.

Conclusion: The worse profile and prognosis observed among patients who recently emigrated from the Soviet Union cannot be explained by traditional risk factors for CAD[2] such as smoking, diabetes, hypertension, and lipid disorders. Further investigation, including variables such as psychological stress to which immigrants are more exposed than others, is needed.

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Intractable forms of autoimmune diseases follow a rapid course, with a significantly shortened life expectancy sometimes comparable to that of malignant diseases. Immunoablative therapy, including high dose cytotoxic agents and hematopoietic autologous stem cell rescue, was recently introduced as an aggressive approach to treat autoimmune diseases that have a rapid course and are resistant to conventional therapy. The most frequent indication for this type of treatment is multiple sclerosis, seconded by systemic sclerosis. The results of immunoablative treatment with documented responses in both diseases are encouraging. The data are mature enough to begin comparative randomized studies of immunoablative versus conventional treatment to validate the benefit of the aggressive approach. A randomized trial involving SSc[1] was recently launched (ASTIS) and a trial involving MS[2] is under preparation. Considerably less experience with immunoablative treatment has been gained in systemic lupus erythematosus, rheumatoid arthritis, and other disorders with an autoimmune pathophysiology. Autologous hematopoietic stem cell transplantation in humans offers more long-lasting immunosuppression than reeducation of lymphocytes. In fact, allogeneic transplantation may replace the whole immune system. However, this attractive approach is still associated with considerable morbidity and mortality and is not yet justified for treatment of automimmune diseases. Non-myeloablative allogeneic transplantation and sub-myeloblative high dose cyclophosphamide without stem cell support are alternative approaches that could be explored in pilot studies.

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