Atherothrombosis is a multifactorial disease and risk factors for atherothrombosis are now estimated to be in the hundreds. In addition to classical risk factors like serum lipids (total cholesterol and triglycerides), lipoproteins (including lipoprotein[a]), apolipoproteins, and a variety of other factors such as infections with corresponding antibodies, autoimmune constituents with corresponding antibodies, inflammatory molecules such as C-reactive protein (CRP), and hemostatic factors have been also considered for risk. Over the past year, we carried out several collaborative studies: (1) In a pilot trial, the effects of thyroid hormones on CRP and hemostasis were assessed in thyroid cancer patients receiving thyroid hormone suppression therapy. At the time of their thyroid scanning, these patients change their thyroid status from extreme hyperthyroid to hypothyroid and back. While on thyroid hormone suppression therapy, the majority of patients exhibited elevated CRP and a prothrombotic profile. These findings are consistent with an increased incidence of atherothrombotic events in hyperthyroidism. (2) In a retrospective study, a large cohort of systemic lupus erythematosus patients (>200) from Johns Hopkins University was evaluated for serum lipoprotein(a) levels (measured by two analytically valid [isoform-independent] methods) and for apolipoprotein(a) isoforms (phenotypes). Data are now being analyzed with respect to association with premature thromboembolic events and other clinical and/or laboratory parameters. If our earlier observation that the presence of medium-sized apolipoprotein(a) isoforms is significantly associated with premature thromboembolic events (164 NIH patients with systemic lupus erythematosus) is validated in a larger, independent patient population, phenotyping for apolipoprotein(a) could become a major tool for identifying systemic lupus erythematosus patients with high risk of atherothrombosis and appropriate prophylactic therapy may be implemented. (3) In other studies: (a) Increased levels of heat-shock protein 70 were associated with low risk of coronary artery disease, while serum antibodies to heat-shock protein 65 correlated with increased coronary calcification. The findings suggest pathogen-triggered autoimmunity in early atherosclerosis and support the view that atherothrombosis is an inflammatory, infectious and/or autoimmune disease. (b) Metabolic syndrome (including elevated CRP) was found in a subset of women with major depressive disorder. This may explain, at least in part, the increased cardiovascular morbidity in these patients.
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