Of 44 competent patients, 33 study patients had received pre-transplantation statin therapy, and 11 control patients had not

Of 44 competent patients, 33 study patients had received pre-transplantation statin therapy, and 11 control patients had not. Pathologic examination of each explanted Hoechst 33342 analog heart confirmed coronary artery disease and previous myocardial infarction in all patients. cross-sections in the control group (range, 1C20 per patient) and 153 cross-sections in the study group (range, 1C12 per patient). The mean quantity of cross-sections per individual was not significantly different between the 2 groups (control, 6.4; study, 5.8; em P /em =0.83). All patients experienced plaques. All control patients experienced at least 1 high-grade plaque (imply, 4.2 per patient; range, 1C18), compared with a mean of 1 1.9 per patient in the study group (range, 1C5; Fig. 3). High-grade lesions were found in 66.3% of cross-sections in the control group, and in 34.6% in the study group ( em P /em =0.011). Conversely, low-grade fibrous plaques (grades 1 and 2) were more frequent in the study group than in the control group (45.7% of cross-sections vs 11.3%; em P /em =0.006). Grade 3, while not considered to be an at-risk lesion, Rabbit Polyclonal to OR1L8 was not included in this comparison. Open in a separate window Fig. 3 Graph shows the number of high-grade plaques per patient in the control and study groups. Immunohistochemical Pathologic Findings All 25 cross-sections of coronary arteries with high-grade plaques that we stained for T-cell and macrophage antigens were positive for both markers; however, the degree of inflammation was markedly lower in the study group. Discussion The transition from stable CAD to acute coronary syndrome (unstable angina, MI, or sudden death) is generally preceded by hemorrhage into a plaque, or by thrombosis that is brought on by rupture or erosion of a vulnerable plaque.7,21,22,25,26 Matrix metalloprotein-ases and cytokines are overexpressed in atheromas by macrophages and smooth-muscle cells. Endothelial cell dysfunction, a paucity of smooth-muscle cells, inflammation, and mechanical stress are associated with increased plaque instability.7,27,28 Vulnerable plaques, particularly in the presence of systemic inflammation, are responsible for most cases of acute coronary syndrome.22,29,30 Furthermore, invasive and noninvasive testing in patients with acute coronary syndrome has shown that many have more than 1 vulnerable plaque.29C31 The risk of progression of untreated vulnerable plaques is unclear, because data are scarce around the natural history. However, statin therapy reduces the incidence of acute coronary complications in at-risk patientsnot only in those with hypercholesterolemia,32 but also in patients who have normal levels of cholesterol.33C35 This suggests that statins reduce or eliminate the presence of vulnerable plaques. In addition, numerous studies have shown that statins reduce total and LDL cholesterol and that they function through a variety of mechanisms.8,10,36C39 Statin therapy produces observable changes after relatively short periods of treatment. Animal and tissue-culture studies have revealed detectable effects after 24 to 72 hours of initial statin treatment.14C16,40 Statin therapy enhances endothelial cell function in human beings within 1 month41 and produces clinically important effects within 6 months.7,8,10,42 The large-scale Scandinavian Simvastatin Survival Study documented an average reduction in total cholesterol of 28% and a reduction in LDL cholesterol of 38% after 6 weeks of statin therapy.32 Limitations of the Study There were several limitations to our study. It was retrospective and with a relatively small number of control cases, chiefly due to the low quantity of heart transplantations that were performed at our institution for end-stage CAD in the Hoechst 33342 analog pre-statin era. The older cases that met the study criteria and experienced suitable pathologic material available for evaluation were small in number yet sufficient to show a statistically significant difference between the 2 groups. Although both groups received aspirin, other medications and their dosages varied among patients: pravastatin was the most commonly used statin in the study group before 1999 (82% of patients), and atorvastatin was the most common thereafter (56% of patients). The length of time from first MI to Hoechst 33342 analog transplantation diverse among patients. Measurements of cholesterol levels before patients’ placement around the transplantation waiting list were not available. At explantation, the hearts experienced undergone routine surgical pathologic examination that was not part of a study protocol. Conclusions Limitations to the study notwithstanding, our findings support the conclusion that vulnerable plaques will stabilize as a result of statin therapyand, in addition, we might infer that lowering cholesterol via other therapies does not confer the same beneficial effects on plaque morphology as does statin therapy. Even though the levels of total and LDL cholesterol were not significantly.

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